Foxo3介导的生理细胞竞争确保了脊椎动物发育过程中稳健的组织模式-动脉网

Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development

Nature 等信源发布 2024-12-17 20:08



可切换为仅中文







AbstractUnfit cells with defective signalling or gene expression are eliminated through competition with neighbouring cells. However, physiological roles and mechanisms of cell competition in vertebrates remain unclear. In addition, universal mechanisms regulating diverse cell competition are unknown.

摘要通过与邻近细胞的竞争，消除了信号传导或基因表达缺陷的不适合细胞。然而，脊椎动物细胞竞争的生理作用和机制仍不清楚。此外，调节多种细胞竞争的普遍机制尚不清楚。

Using zebrafish imaging, we reveal that cell competition ensures robust patterning of the spinal cord and muscle through elimination of cells with unfit sonic hedgehog activity, driven by cadherin-mediated communication between unfit and neighbouring fit cells and subsequent activation of the Smad-Foxo3-reactive oxygen species axis.

使用斑马鱼成像，我们揭示了细胞竞争通过消除具有不适合的声波刺猬活性的细胞来确保脊髓和肌肉的稳健模式，这是由钙粘蛋白介导的不适合和相邻fit细胞之间的通讯以及随后激活Smad-Foxo3-活性氧物质轴驱动的。

We identify Foxo3 as a common marker of loser cells in various types of cell competition in zebrafish and mice. Foxo3-mediated physiological cell competition is required for eliminating various naturally generated unfit cells and for the consequent precise patterning during zebrafish embryogenesis and organogenesis.

我们将Foxo3鉴定为斑马鱼和小鼠各种细胞竞争中输家细胞的常见标记。Foxo3介导的生理细胞竞争是消除各种天然产生的不适合细胞以及斑马鱼胚胎发生和器官发生过程中随之而来的精确模式所必需的。

Given the implication of Foxo3 downregulation in age-related diseases, cell competition may be a defence system to prevent abnormalities throughout development and adult homeostasis..

鉴于Foxo3下调在与年龄相关的疾病中的意义，细胞竞争可能是一种防御系统，可以防止整个发育和成人体内平衡异常。。

IntroductionAnimal development is highly reproducible and repeatedly generates tissues and organs with the same function. An appropriate number of cells with specific functions must be located at the correct positions to construct functional tissues and organs. Such spatial cell arrangements are regulated by genetic information and the corresponding biochemical signals1,2.

引言动物发育具有高度可重复性，可重复产生具有相同功能的组织和器官。必须将适当数量的具有特定功能的细胞定位在正确的位置，以构建功能性组织和器官。这种空间细胞排列受遗传信息和相应的生化信号调控1,2。

However, dynamic morphogenesis, including active rapid cell proliferation and migration during development, may induce replication errors and cellular signalling perturbations, generating unfit cells in developing tissues. Recent advances in single-cell analyses have revealed frequent generation of cells with somatic mutations or chromosome segregation errors during normal human and mouse embryogenesis3,4,5,6.

然而，动态形态发生，包括发育过程中活跃的快速细胞增殖和迁移，可能会引起复制错误和细胞信号扰动，从而在发育中的组织中产生不适合的细胞。单细胞分析的最新进展表明，在正常人和小鼠胚胎发生过程中，频繁产生具有体细胞突变或染色体分离错误的细胞3,4,5,6。

Our zebrafish imaging analysis also showed frequent occurrence of unfit cells with abnormal Wnt/β-catenin activity in normal embryos7. Considering the fact that developing animals achieve reproducible construction of functional tissues and organs, they must possess systems to overcome the generation of such unfit cells.

我们的斑马鱼成像分析还显示，正常胚胎中经常出现Wnt/β-连环蛋白活性异常的不适合细胞7。考虑到发育中的动物可以实现功能性组织和器官的可重复构建，它们必须拥有克服这种不适合细胞产生的系统。

However, the mechanisms underlying robust tissue development are not completely understood.Cell competition may support conquering unfit cell appearance during early embryogenesis. Cell competition is a cell–cell interactive process for removing less fit viable cells, which was discovered in Drosophila8,9.

然而，强大组织发育的潜在机制尚不完全清楚。细胞竞争可能支持在早期胚胎发生过程中克服不适合的细胞外观。细胞竞争是一种细胞间相互作用的过程，用于去除不太适合的活细胞，这是在果蝇中发现的8,9。

Unfit cells with relatively low Myc expression, Yap activity, or mitochondrial defects spontaneously arise during early mouse embryogenesis; however, these cells are eliminated through competitive communication with neighbouring normal cells10,11,12. Furthermore, cell competition corrects the noisy Wnt/β-catenin morphogen gradient, which patterns the zebrafish embryonic anterio.

在小鼠早期胚胎发生过程中，Myc表达相对较低，Yap活性或线粒体缺陷的不适合细胞自发产生；然而，这些细胞通过与邻近正常细胞的竞争性通信而被消除10,11,12。。

foxo3b-mediated elimination of unfit cells is essential for precise developmentBecause unfit cells with abnormal Wnt/β-catenin, Shh activity, or dbx1b expression spontaneously appear during embryogenesis and organogenesis, we also confirmed that foxo3b expression was upregulated in naturally generated Wnt-, Shh-, or dbx1b-unfit cells (Supplementary Fig. 9a–c).

foxo3b介导的不适合细胞的消除对于精确发育至关重要，因为在胚胎发生和器官发生过程中自发出现具有异常Wnt/β-连环蛋白，Shh活性或dbx1b表达的不适合细胞，我们还证实foxo3b表达在天然产生的Wnt，Shh或dbx1b不适合细胞中上调（补充图9a-c）。

We generated transgenic zebrafish Tg(foxo3b:GFP) and Tg(foxo3b:mCherry), which expresses GFP or mCherry in cells expressing endogenous foxo3b to further examine foxo3b-positive unfit cells during development (Supplementary Fig. 9d, e). foxo3b-positive cells appeared spontaneously in early embryos (Supplementary Fig. 9f; Supplementary Movie 3) and in the developing spinal cord and muscle primordia (Supplementary Fig. 9g).

我们产生了转基因斑马鱼Tg（foxo3b:GFP）和Tg（foxo3b:mCherry），它们在表达内源性foxo3b的细胞中表达GFP或mCherry，以进一步检查发育过程中foxo3b阳性不适合的细胞（补充图9d，e）。foxo3b阳性细胞在早期胚胎（补充图9f；补充电影3）以及发育中的脊髓和肌肉原基（补充图9g）中自发出现。

The number and position of foxo3b-positive cells varied among the individuals (Supplementary Fig. 9f, g), indicating that foxo3b upregulation is not pre-programmed. Moreover, some foxo3b-positive cells activated caspase-3 (Supplementary Fig. 9f, g; Supplementary Movie 3), and the inhibition of apoptosis-induced foxo3b-positive cell accumulation (Supplementary Fig. 9h).

foxo3b阳性细胞的数量和位置在个体之间有所不同（补充图9f，g），表明foxo3b上调不是预先编程的。此外，一些foxo3b阳性细胞激活了caspase-3（补充图9f，g；补充电影3），并且抑制了凋亡诱导的foxo3b阳性细胞积累（补充图9h）。

These results suggest that the foxo3b reporter zebrafsih can be used to visualise naturally emerging unfit cells which are eliminated through cell competition.To evaluate the Foxo3b function under physiological conditions, we inhibited Foxo3b using foxo3bDN mRNA. Overexpression of foxo3bDN did not affect the expression patterns of Wnt morphogen in early embryos and Shh morphogen in developing organs (Supplementary Fig. 10a, b), whereas it induced accumulation of Wnt signalling-unfit cells (Supplementary Fig. 10c) and ectopic activation or inactivation of a Wnt signalling-target posterior gene cdx453 (Supplementary Fig. 10d) in early.

这些结果表明，foxo3b报告基因zebrafsih可用于可视化通过细胞竞争消除的自然出现的不适合细胞。为了评估生理条件下Foxo3b的功能，我们使用foxo3bDN mRNA抑制Foxo3b。foxo3bDN的过表达不影响早期胚胎中Wnt形态发生素和发育器官中Shh形态发生素的表达模式（补充图10a，b），而它诱导Wnt信号传导不适合细胞的积累（补充图10c）和Wnt信号传导靶向后基因cdx453的异位激活或失活（补充图10d）。

foxo3b KO zebrafish in F0 generationCas9 and four sgRNAs were injected into one-cell stage embryos to generate foxo3b KO zebrafish in F0 generation54,55,56. The sgRNA sequences were as follows: 5′- ccggcgaagggccaaaaatgggg-3′, 5′- gacggaggcttcccggcgaaggg-3′, and 5′-ggattcagcaaccccatttttgg-3′, 5′- gcgtagacggtagttttgagagg-3′.

。sgRNA序列如下：5'-ccggcgaagggccaaaaatgggg-3'，5'-GACGGAGGCTTCCGGCGAAGGG-3'和5'-GGATTCAGCAACCCATTTTGG-3'，5'-GCGTAGACGGTAGTTTGAGAGG-3'。

As control, four luciferase sgRNAs were injected; their sequences were as follows: 5′-gggcatttcgcagcctaccgtgg-3′, 5′-ggcatgcgagaatctcacgcagg-3′, and 5′-tcggggaagcggttgccaagagg-3′, and 5′- tttgtggacgaagtaccgaaagg-3′.Mosaic or ubiquitous introduction of rps3 mutant cellsCas9 mRNA and sgRNAs were injected into a single blastomere of an eight-cell stage embryo to introduce mosaic mutants99.

作为对照，注射了四种荧光素酶sgRNA；它们的序列如下：5'-GGGCATTTCGCAGCTACCGTGG-3'，5'-ggcatgcgagaatctcacgcagg-3'和5'-TCGGGGAAGCGGTTGCCAAGAG-3'和5'-tttgtggacgaagtaccgaaagg-3'。rps3突变细胞的镶嵌或无处不在的引入将sCas9 mRNA和sgRNA注射到八细胞期胚胎的单个卵裂球中以引入镶嵌突变体99。

Cas9 mRNA and sgRNAs were injected into one-cell stage embryos to generate ubiquitous mutants99. Three sgRNAs were injected to disrupt the rps3 gene efficiently54,56. The sgRNA sequences were as follows: 5′-cgaggatggttattccggcgtgg-3′, 5′-cattcgtgagctgaccgctgtgg-3′, and 5′-tctctgcgctacaagctgctcgg-3′.Time-lapse imaging and data analysisFor time-lapse confocal live imaging, larvae with mosaically introduced SmoCA cells (Supplementary Movie 1, 2) or Tg(foxo3b:mCherry) embryos (Supplementary Movie 3) were manually dechorionated using forceps and mounted in 1% low melting agarose with egg water onto glass bottom dishes.

将Cas9 mRNA和sgRNA注射到单细胞期胚胎中以产生无处不在的突变体99。注射三种sgRNA以有效破坏rps3基因54,56。sgRNA序列如下：5'-cgaggatggttattccggcgtgg-3'，5'-CATTCGTGAGCTGACCGCTGG-3'和5'-tctctgcgctacaagctgctcgg-3'。延时成像和数据分析对于延时共聚焦实时成像，使用镊子手动去除镶嵌引入的SmoCA细胞（补充电影1,2）或Tg（foxo3b:mCherry）胚胎（补充电影3）的幼虫，并将其安装在1%低熔点琼脂糖中，并将蛋水置于玻璃底皿中。

Live imaging was performed using an FV3000 confocal laser scanning microscope (Olympus, Tokyo, Japan). In Supplementary Movie 1, 2, two laser lines at 488 and 594 nm were used. The recording interval was 10 min. At each time point, 30 confocal slices were acquired along the z-axis. In Supplementary Movie 3, three lase lines at 445, 488, and 561 nm were used.

使用FV3000共聚焦激光扫描显微镜（Olympus，Tokyo，Japan）进行实时成像。在补充电影1,2中，使用了488和594 nm的两条激光线。记录间隔为10分钟。在每个时间点，沿z轴采集30个共聚焦切片。在补充电影3中，使用了445488和561nm的三条激光线。

The recording interval was 10 min. At each time point, 18 confocal slices were acquired along the z-ax.

记录间隔为10分钟。在每个时间点，沿z轴采集18个共聚焦切片。

Data availability

数据可用性

All the data supporting this study are available within the article, supplementary information, and source data. The previously published datasets re-analyzed in this work can be accessed as GSE133526 and E-MTAB-80-640. Source data are provided with this paper.

支持这项研究的所有数据都可以在文章，补充信息和源数据中找到。在这项工作中重新分析的先前发布的数据集可以作为GSE133526和E-MTAB-80-640访问。本文提供了源数据。

ReferencesWolpert, L. Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol. 25, 1–47 (1969).Article

参考文献Wolpert，L。位置信息和细胞分化的空间模式。J、理论。生物学25,1-47（1969）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Davidson, E. H. Emerging properties of animal gene regulatory networks. Nature 468, 911–920 (2010).Article

Davidson，E.H。动物基因调控网络的新兴特性。《自然》468911–920（2010）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Ju, Y. S. et al. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. Nature 543, 714–718 (2017).Article

Ju，Y.S.等人。体细胞突变揭示了早期人类胚胎中不对称的细胞动力学。自然543714-718（2017）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Jónsson, H. et al. Multiple transmissions of de novo mutations in families. Nat. Genet. 50, 1674–1680 (2018).Article

Jónsson，H.等人。家族中从头突变的多次传播。纳特·吉内特。501674-1680（2018）。文章

PubMed

Google Scholar

谷歌学者

Mashiko, D. et al. Chromosome segregation error during early cleavage in mouse pre-implantation embryo does not necessarily cause developmental failure after blastocyst stage. Sci. Rep. 10, 854 (2020).Article

Mashiko，D。等人。小鼠植入前胚胎早期卵裂过程中的染色体分离错误不一定会导致胚泡期后的发育失败。科学。代表10854（2020）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Currie, C. E. et al. The first mitotic division of human embryos is highly error prone. Nat. Commun. 13, 6755 (2022).Article

Currie，C.E。等人。人类胚胎的第一次有丝分裂非常容易出错。国家公社。136755（2022年）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Akieda, Y. et al. Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo. Nat. Commun. 10, 4710 (2019).Article

Akieda，Y。等人。细胞竞争校正了嘈杂的Wnt形态发生梯度，以在斑马鱼胚胎中实现强大的模式。国家公社。104710（2019）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Morata, G. & Ripoll, P. Minutes: mutants of drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975).Article

Morata，G。＆Ripoll，P。Minutes：果蝇突变体自主影响细胞分裂率。开发生物。42211-221（1975）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Bowling, S., Lawlor, K. & Rodríguez, T. A. Cell competition: the winners and losers of fitness selection. Development 146, dev167486 (2019).Article

Bowling，S.，Lawlor，K.＆Rodríguez，T.A。Cell competition：健身选择的赢家和输家。发展146，dev167486（2019）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Clavería, C., Giovinazzo, G., Sierra, R. & Torres, M. Myc-driven endogenous cell competition in the early mammalian embryo. Nature 500, 39–44 (2013).Article

Clavería，C.，Giovinazzo，G.，Sierra，R。＆Torres，M。Myc在早期哺乳动物胚胎中驱动内源性细胞竞争。《自然》500,39-44（2013）。文章

ADS

PubMed

Google Scholar

谷歌学者

Hashimoto, M. & Sasaki, H. Epiblast formation by TEAD-YAP-dependent expression of pluripotency factors and competitive elimination of unspecified cells. Dev. Cell 50, 139–154.e5 (2019).Article

Hashimoto，M。＆Sasaki，H。通过TEAD-YAP依赖性表达多能性因子和竞争性消除未指定细胞形成外胚层。Dev.Cell 50139–154.e5（2019）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Lima, A. et al. Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development. Nat. Metab. 3, 1091–1108 (2021).Article

Lima，A。等人。细胞竞争作为一种纯化选择，在小鼠早期发育过程中消除线粒体缺陷的细胞。自然代谢。31091-1108（2021）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Hogan, C. et al. Characterization of the interface between normal and transformed epithelial cells. Nat. Cell Biol. 11, 460–467 (2009).Article

Hogan，C.等人。正常和转化上皮细胞之间界面的表征。自然细胞生物学。11460-467（2009）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Kajita, M. et al. Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells. J. Cell Sci. 123, 171–180 (2010).Article

Kajita，M。等人。与周围正常上皮细胞的相互作用影响Src转化细胞的信号传导途径和行为。J、细胞科学。123171-180（2010）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Haraoka, Y., Akieda, Y., Nagai, Y., Mogi, C. & Ishitani, T. Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis. Nat. Commun. 13, 1417 (2022).Article

Haraoka，Y.，Akieda，Y.，Nagai，Y.，Mogi，C。＆Ishitani，T。斑马鱼成像揭示了TP53突变在原发性肿瘤发生中将癌基因诱导的衰老从抑制因子转换为驱动因子。国家公社。131417（2022）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Rhiner, C. et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in drosophila. Dev. Cell 18, 985–998 (2010).Article

花形成了一种细胞外密码，揭示了果蝇细胞与其邻居的适应性。Dev.Cell 18985–998（2010）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Merino, M. M. et al. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell 160, 461–476 (2015).Article

Merino，M.M。等人。消除不适合的细胞可以维持组织健康并延长寿命。细胞160461-476（2015）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Meyer, S. N. et al. An ancient defense system eliminates unfit cells from developing tissues during cell competition. Science 346, 1258236 (2014).Article

Meyer，S.N.等人。一种古老的防御系统可以在细胞竞争过程中从发育中的组织中消除不适合的细胞。科学3461258236（2014）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Alpar, L., Bergantiños, C. & Johnston, L. A. Spatially restricted regulation of spätzle/toll signaling during cell competition. Dev. Cell 46, 706–719.e5 (2018).Article

Alpar，L.，Bergantiños，C。＆Johnston，L.A。在细胞竞争过程中对spätzle/toll信号传导的空间限制性调节。Dev.Cell 46706–719.e5（2018）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Nagata, R., Nakamura, M., Sanaki, Y. & Igaki, T. Cell competition is driven by autophagy. Dev. Cell 51, 99–112.e4 (2019).Article

Nagata，R.，Nakamura，M.，Sanaki，Y。＆Igaki，T。细胞竞争是由自噬驱动的。开发单元51,99-112.e4（2019）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Katsukawa, M., Ohsawa, S., Zhang, L., Yan, Y. & Igaki, T. Serpin facilitates tumor-suppressive cell competition by blocking toll-mediated Yki activation in drosophila. Curr. Biol. 28, 1756–1767.e6 (2018).Article

Katsukawa，M.，Ohsawa，S.，Zhang，L.，Yan，Y。＆Igaki，T。Serpin通过阻断果蝇中toll介导的Yki激活来促进肿瘤抑制性细胞竞争。货币。生物学281756-1767.e6（2018）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Novitch, B. G., Chen, A. I. & Jessell, T. M. Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2. Neuron 31, 773–789 (2001).Article

Novitch，B.G.，Chen，A.I。＆Jessell，T.M。通过bHLH阻遏物Olig2协调运动神经元亚型同一性和泛神经元特性的调节。神经元31773-789（2001）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Pierani, A. et al. Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron 29, 367–384 (2001).Article

Pierani，A.等人。祖细胞同源结构域蛋白Dbx1对发育中脊髓中间神经元命运的控制。神经元29367-384（2001）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Park, H.-C., Mehta, A., Richardson, J. S. & Appel, B. olig2 is required for zebrafish primary motor neuron and oligodendrocyte development. Dev. Biol. 248, 356–368 (2002).Article

Park，H.-C.，Mehta，A.，Richardson，J.S。＆Appel，B。olig2是斑马鱼原代运动神经元和少突胶质细胞发育所必需的。开发生物。248356-368（2002）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Gribble, S. L., Nikolaus, O. B. & Dorsky, R. I. Regulation and function of Dbx genes in the zebrafish spinal cord. Dev. Dyn. Off. Publ. Am. Assoc. Anat. 236, 3472–3483 (2007).CAS

Gribble，S.L.，Nikolaus，O.B。和Dorsky，R.I。斑马鱼脊髓中Dbx基因的调节和功能。开发动态。关闭。公开。美国安那州协会。2363472-3483（2007）。中科院

Google Scholar

谷歌学者

Lek, M. et al. A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning. Development 137, 4051–4060 (2010).Article

Lek，M。等人。同源域反馈电路是腹侧神经图案化过程中Shh形态发生梯度的阶跃函数解释的基础。发展1374051-4060（2010）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Devoto, S. H., Melançon, E., Eisen, J. S. & Westerfield, M. Identification of separate slow and fast muscle precursor cells in vivo, prior to somite formation. Development 122, 3371–3380 (1996).Article

Devoto，S.H.，Melançon，E.，Eisen，J.S。＆Westerfield，M。在体节形成之前，在体内鉴定单独的慢速和快速肌肉前体细胞。发展1223371-3380（1996）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Stickney, H. L., Barresi, M. J. & Devoto, S. H. Somite development in zebrafish. Dev. Dyn. Off. Publ. Am. Assoc. Anat. 219, 287–303 (2000).CAS

Stickney，H.L.，Barresi，M.J。和Devoto，S.H。斑马鱼的体节发育。开发动态。关闭。公开。美国安那州协会。219287-303（2000）。中科院

Google Scholar

谷歌学者

Blagden, C. S., Currie, P. D., Ingham, P. W. & Hughes, S. M. Notochord induction of zebrafish slow muscle mediated by Sonic hedgehog. Genes Dev. 11, 2163–2175 (1997).Article

。Genes Dev.112163–2175（1997）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1, 20–29 (2000).Article

Jessell，T.M。脊髓中的神经元规范：诱导信号和转录代码。Genet自然Rev。1，20-29（2000）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Dessaud, E., McMahon, A. P. & Briscoe, J. Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development 135, 2489–2503 (2008).Article

Dessaud，E.，McMahon，A.P。＆Briscoe，J。脊椎动物神经管中的模式形成：声波刺猬形态发生素调节的转录网络。发展1352489-2503（2008）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Ueda, Y., Shimizu, Y., Shimizu, N., Ishitani, T. & Ohshima, T. Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury. J. Comp. Neurol. 526, 2360–2372 (2018).Article

Ueda，Y.，Shimizu，Y.，Shimizu，N.，Ishitani，T。＆Ohshima，T。刺伤后成年斑马鱼视顶盖再生神经发生中声波刺猬和notch信号的参与。J、公司。神经病学。5262360-2372（2018）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Incardona, J. P., Gaffield, W., Kapur, R. P. & Roelink, H. The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic hedgehog signal transduction. Development 125, 3553–3562 (1998).Article

Incardona，J.P.，Gaffield，W.，Kapur，R.P。＆Roelink，H。致畸藜芦生物碱环巴胺抑制声波刺猬信号转导。发展1253553-3562（1998）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Tsai, T. Y.-C. et al. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science 370, 113–116 (2020).Article

Tsai，T.Y.-C.等人。粘附代码确保在组织形态发生过程中形成强大的图案。科学370113-116（2020）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Lele, Z. et al. parachute / n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube. Development 129, 3281–3294 (2002).Article

Lele，Z。等人。降落伞/n-钙粘蛋白是斑马鱼神经管形态发生和维持完整性所必需的。发展1293281-3294（2002）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Franklin, J. L. & Sargent, T. D. Ventral neural cadherin, a novel cadherin expressed in a subset of neural tissues in the zebrafish embryo. Dev. Dyn. 206, 121–130 (1996).Article

Franklin，J.L。＆Sargent，T.D。腹侧神经钙粘蛋白，一种在斑马鱼胚胎的一部分神经组织中表达的新型钙粘蛋白。开发动态。206121-130（1996）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Sun, Y., Tseng, W.-C., Fan, X., Ball, R. & Dougan, S. T. Extraembryonic signals under the control of MGA, Max, and Smad4 are required for dorsoventral patterning. Dev. Cell 28, 322–334 (2014).Article

Sun，Y.，Tseng，W.-C.，Fan，X.，Ball，R。＆Dougan，S.T。背腹模式需要在MGA，Max和Smad4控制下的胚外信号。Dev.Cell 28322–334（2014）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Carter, M. E. & Brunet, A. FOXO transcription factors. Curr. Biol. 17, R113–R114 (2007).Article

Carter，M.E。和Brunet，A。FOXO转录因子。货币。生物学17，R113-R114（2007）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Xie, X., Liu, J.-X., Hu, B. & Xiao, W. Zebrafish foxo3b negatively regulates canonical Wnt signaling to affect early embryogenesis. PLoS ONE 6, e24469 (2011).Article

Xie，X.，Liu，J.-X.，Hu，B。＆Xiao，W。斑马鱼foxo3b负调节经典Wnt信号传导以影响早期胚胎发生。《公共科学图书馆·综合》第6期，第24469页（2011年）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Nogueira, V. et al. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14, 458–470 (2008).Article

Nogueira，V。等人Akt确定复制性衰老和氧化或致癌过早衰老，并使细胞对氧化性凋亡敏感。癌细胞14458-470（2008）。文章

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Han, J. et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc. Natl Acad. Sci. USA 98, 11318–11323 (2001).Article

Han，J。等人。bbc3（一种仅促凋亡BH3的基因）的表达受多种细胞死亡和存活信号的调节。程序。国家科学院。科学。美国9811318-11323（2001）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Nakano, K. & Vousden, K. H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell 7, 683–694 (2001).Article

Nakano，K。＆Vousden，K。H。PUMA是一种新型的促凋亡基因，由p53诱导。分子细胞7683-694（2001）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W. & Vogelstein, B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell 7, 673–682 (2001).Article

Yu，J.，Zhang，L.，Hwang，P.M.，Kinzler，K.W。＆Vogelstein，B.PUMA诱导结直肠癌细胞的快速凋亡。分子细胞7673-682（2001）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

You, H. et al. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. J. Exp. Med. 203, 1657–1663 (2006).Article

You，H。等人。FOXO3a依赖性调节Puma对细胞因子/生长因子戒断的反应。J、实验医学2031657-1663（2006）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

You, H., Yamamoto, K. & Mak, T. W. Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a. Proc. Natl Acad. Sci. USA 103, 9051–9056 (2006).Article

You，H.，Yamamoto，K。＆Mak，T。W。通过FOXO3a调节p53的反式激活非依赖性促凋亡活性。程序。国家科学院。科学。美国1039051–9056（2006）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Tucka, J. et al. Akt1 regulates vascular smooth muscle cell apoptosis through FoxO3a and Apaf1 and protects against arterial remodeling and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 34, 2421–2428 (2014).Article

塔卡，J。等人。Akt1通过FoxO3a和Apaf1调节血管平滑肌细胞凋亡，并防止动脉重塑和动脉粥样硬化。动脉硬化。血栓。Vasc。生物学342421-2428（2014）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Boldin, M. P., Goncharov, T. M., Goltseve, Y. V. & Wallach, D. Involvement of MACH, a Novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor–induced cell death. Cell 85, 803–815 (1996).Article

Boldin，M.P.，Goncharov，T.M.，Goltseve，Y.V。＆Wallach，D。新型MORT1/FADD相互作用蛋白酶MACH参与Fas/APO-1和TNF受体诱导的细胞死亡。细胞85803-815（1996）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Muzio, M. et al. FLICE, a novel FADD-Homologous ICE/CED-3–like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85, 817–827 (1996).Article

Muzio，M。等人FLICE是一种新型FADD同源ICE/CED-3样蛋白酶，被募集到CD95（Fas/APO-1）死亡诱导信号复合物中。细胞85817-827（1996）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Alessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A. & Cohen, P. Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase‐1 and p70 S6 kinase. FEBS Lett. 399, 333–338 (1996).Article

Alessi，D.R.，Barry Caudwell，F.，Andjelkovic，M.，Hemmings，B.A。＆Cohen，P。蛋白激酶B底物特异性的分子基础；与MAPKAP激酶-1和p70 S6激酶的比较。。399333-338（1996）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Brunet, A. et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96, 857–868 (1999).Article

Brunet，A。等人。Akt通过磷酸化和抑制叉头转录因子来促进细胞存活。细胞96857-868（1999）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Lützner, N., Kalbacher, H., Krones-Herzig, A. & Rösl, F. FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own expression based on cellular AMP levels via a positive autoregulatory loop. PLoS ONE 7, e42166 (2012).Article

Lützner，N.，Kalbacher，H.，Krones-Herzig，A。＆Rösl，F。FOXO3是糖皮质激素受体靶标，并通过正向自动调节环基于细胞AMP水平调节LKB1及其自身表达。PLoS ONE 7，e42166（2012）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Seoane, J., Le, H.-V., Shen, L., Anderson, S. A. & Massagué, J. Integration of Smad and Forkhead Pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117, 211–223 (2004).Article

Seoane，J.，Le，H.-V.，Shen，L.，Anderson，S.A。＆Massagué，J。Smad和叉头通路在控制神经上皮和胶质母细胞瘤细胞增殖中的整合。细胞117211-223（2004）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Joly, J.-S. et al. Expression of a zebrafish caudal homeobox gene correlates with the establishment of posterior cell lineages at gastrulation. Differentiation 50, 75–87 (1992).Article

Joly，J.-S.等人。斑马鱼尾部同源框基因的表达与原肠胚形成时后细胞谱系的建立相关。分化50,75-87（1992）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Sunagawa, G. A. et al. Mammalian reverse genetics without crossing reveals Nr3a as a short-sleeper gene. Cell Rep. 14, 662–677 (2016).Article

Sunagawa，G.A。等人，《哺乳动物无杂交反向遗传学》揭示Nr3a是一个短睡眠基因。Cell Rep.14662–677（2016）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Wu, R. S. et al. A rapid method for directed gene knockout for screening in G0 Zebrafish. Dev. Cell 46, 112–125.e4 (2018).Article

Wu，R.S.等人。用于筛选G0斑马鱼的定向基因敲除的快速方法。Dev.Cell 46112–125.e4（2018）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Suzuki, H. et al. De novo non-synonymous CTR9 variants are associated with motor delay and macrocephaly: human genetic and zebrafish experimental evidence. Hum. Mol. Genet. 31, 3846–3854 (2022).Article

Suzuki，H。等人。从头开始的非同义CTR9变体与运动延迟和大头畸形有关：人类遗传和斑马鱼实验证据。嗯，摩尔·吉内特。313846-3854（2022）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Kon, S. et al. Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. Nat. Cell Biol. 19, 530–541 (2017).Article

Kon，S.等人。与正常上皮细胞的细胞竞争通过代谢变化促进转化细胞的顶端挤出。自然细胞生物学。19530-541（2017）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Sancho, M. et al. Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev. Cell 26, 19–30 (2013).Article

Sancho，M。等人。竞争性相互作用在分化开始时消除不适合的胚胎干细胞。Dev.Cell 26,19-30（2013）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Hu, B. et al. Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis. Dev. Biol. 388, 81–93 (2014).Article

Hu，B。等人。斑马鱼eaf1抑制foxo3b表达，以调节原始造血中gata1和spi1的转录活性。开发生物。388,81-93（2014）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Gao, L. et al. FOXO genes in channel catfish and their response after bacterial infection. Dev. Comp. Immunol. 97, 38–44 (2019).Article

Gao，L。等人。斑点叉尾鮰中的FOXO基因及其在细菌感染后的反应。开发公司。免疫。97,38-44（2019）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Villa del Campo, C., Clavería, C., Sierra, R. & Torres, M. Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Rep. 8, 1741–1751 (2014).Article

Villa del Campo，C.，Clavería，C.，Sierra，R。＆Torres，M。细胞竞争促进哺乳动物心脏中表型沉默的心肌细胞替代。Cell Rep.81741–1751（2014）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Ellis, S. J. et al. Distinct modes of cell competition shape mammalian tissue morphogenesis. Nature 569, 497–502 (2019).Article

Ellis，S.J.等人。不同的细胞竞争模式塑造了哺乳动物的组织形态发生。自然569497-502（2019）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Sun, X.-L. et al. Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development. Dev. Cell 58, 744–759.e11 (2023).Article

Sun，X.-L.等人。由Axin2-p53轴驱动的干细胞竞争控制小鼠发育过程中的大脑大小。开发单元58744-759.e11（2023）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Adachi-Yamada, T., Fujimura-Kamada, K., Nishida, Y. & Matsumoto, K. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature 400, 166–169 (1999).Article

Adachi Yamada，T.，Fujimura Kamada，K.，Nishida，Y。＆Matsumoto，K。近端信息的扭曲导致果蝇翅膀中JNK依赖性细胞凋亡。自然400166-169（1999）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Adachi-Yamada, T. & O’Connor, M. B. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev. Biol. 251, 74–90 (2002).Article

Adachi Yamada，T。＆O'Connor，M.B。形态发生细胞凋亡：纠正形态发生梯度不连续性的机制。开发生物。251,74-90（2002）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Van Den Brink, G. R. et al. Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat. Genet. 36, 277–282 (2004).Article

Van Den Brink，G.R.等人。印度刺猬是结肠上皮细胞分化中Wnt信号传导的拮抗剂。纳特·吉内特。36277-282（2004）。文章

PubMed

Google Scholar

谷歌学者

Farin, H. F. et al. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530, 340–343 (2016).Article

Farin，H.F.等人。肠道干细胞生态位中短程Wnt梯度的可视化。《自然》530340–343（2016）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Wang, C. et al. Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype. J. Clin. Investig. 128, 4343–4358 (2018).Article

Wang，C。等人。刺猬的扩增破坏了间充质的特性并诱导了肺气肿的表型。J、临床。调查。1284343-4358（2018）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Powell, D. R. et al. Cdon promotes neural crest migration by regulating N-cadherin localization. Dev. Biol. 407, 289–299 (2015).Article

Powell，D.R.等人，Cdon通过调节N-钙粘蛋白的定位来促进神经c迁移。开发生物。407289-299（2015）。文章

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Van Der Vos, K. E. & Coffer, P. J. FOXO-binding partners: it takes two to tango. Oncogene 27, 2289–2299 (2008).Article

。癌基因272289-2299（2008）。文章

PubMed

Google Scholar

谷歌学者

Daitoku, H., Sakamaki, J. & Fukamizu, A. Regulation of FoxO transcription factors by acetylation and protein–protein interactions. Biochim. Biophys. Acta BBA - Mol. Cell Res. 1813, 1954–1960 (2011).Article

Daitoku，H.，Sakamaki，J。＆Fukamizu，A。通过乙酰化和蛋白质-蛋白质相互作用调节FoxO转录因子。生物化学。生物物理。《BBA分子细胞研究学报》18131954-1960（2011）。文章

CAS

中科院

Google Scholar

谷歌学者

Calissi, G., Lam, E. W.-F. & Link, W. Therapeutic strategies targeting FOXO transcription factors. Nat. Rev. Drug Discov. 20, 21–38 (2021).Article

Calissi，G.，Lam，E.W.-F。＆Link，W。针对FOXO转录因子的治疗策略。《药物目录》修订版。20,21-38（2021）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Hagenbuchner, J. & Ausserlechner, M. J. Mitochondria and FOXO3: breath or die. Front. Physiol. 4, 147 (2013).Article

Hagenbuchner，J。＆Ausserlechner，M.J。线粒体和FOXO3：呼吸或死亡。正面。生理学。4147（2013）。文章

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Kinzler, K. W. et al. Identification of FAP locus genes from chromosome 5q21. Science 253, 661–665 (1991).Article

Kinzler，K.W.等人。从染色体5q21鉴定FAP基因座基因。科学253661-665（1991）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Nishisho, I. et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253, 665–669 (1991).Article

Nishisho，I。等人。FAP和结直肠癌患者染色体5q21基因突变。科学253665-669（1991）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Oro, A. E. et al. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science 276, 817–821 (1997).Article

。科学276817-821（1997）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Xie, J. et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature 391, 90–92 (1998).Article

Xie，J.等人。激活散发性基底细胞癌中的平滑突变。《自然》391,90-92（1998）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Fei, M. et al. Low expression of Foxo3a is associated with poor prognosis in ovarian cancer patients. Cancer Investig. 27, 52–59 (2009).Article

Fei，M。等人。Foxo3a的低表达与卵巢癌患者的预后不良有关。癌症调查。。文章

CAS

中科院

Google Scholar

谷歌学者

Shou, Z., Lin, L., Liang, J., Li, J.-L. & Chen, H.-Y. Expression and prognosis of FOXO3a and HIF-1α in nasopharyngeal carcinoma. J. Cancer Res. Clin. Oncol. 138, 585–593 (2012).Article

Shou，Z.，Lin，L.，Liang，J.，Li，J.-L.＆Chen，H.-Y.FOXO3a和HIF-1α在鼻咽癌中的表达和预后。J、癌症研究临床。Oncol公司。138585-593（2012）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Willcox, B. J. et al. FOXO3A genotype is strongly associated with human longevity. Proc. Natl Acad. Sci. USA 105, 13987–13992 (2008).Article

Willcox，B.J。等人，FOXO3A基因型与人类寿命密切相关。程序。国家科学院。科学。。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Martins, R., Lithgow, G. J. & Link, W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15, 196–207 (2016).Article

Martins，R.，Lithgow，G.J。＆Link，W。长寿FOXO：揭示FOXO蛋白在衰老和长寿中的作用。衰老细胞15196-207（2016）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Timmers, P. R. H. J., Wilson, J. F., Joshi, P. K. & Deelen, J. Multivariate genomic scan implicates novel loci and haem metabolism in human ageing. Nat. Commun. 11, 3570 (2020).Article

Timmers，P.R.H.J.，Wilson，J.F.，Joshi，P.K。＆Deelen，J。多元基因组扫描暗示了人类衰老中的新基因座和血红素代谢。国家公社。113570（2020）。文章

ADS

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Zhang, W. et al. A single-cell transcriptomic landscape of primate arterial aging. Nat. Commun. 11, 2202 (2020).Article

Zhang，W。等人。灵长类动物动脉衰老的单细胞转录组学景观。国家公社。112202（2020）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Liu, X. et al. Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL). J. Biol. Chem. 291, 25692–25705 (2016).Article

Liu，X。等人。叉头转录因子3a（FOXO3a）通过上调von Hippel-Lindau基因（VHL）来调节缺氧信号传导。J、生物。化学。29125692-25705（2016）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Wada, H. et al. Wnt/Dkk negative feedback regulates sensory organ size in Zebrafish. Curr. Biol. 23, 1559–1565 (2013).Article

Wnt/Dkk负反馈调节斑马鱼的感觉器官大小。货币。生物学231559-1565（2013）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Sasaki, H., Hui, C., Nakafuku, M. & Kondoh, H. A binding site for Gli proteins is essential for HNF-3 β floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 124, 1313–1322 (1997).Article

Sasaki，H.，Hui，C.，Nakafuku，M。＆Kondoh，H。Gli蛋白的结合位点对于转基因中的HNF-3β底板增强子活性至关重要，并且可以在体外对Shh产生反应。发展1241313-1322（1997）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Shimizu, N., Kawakami, K. & Ishitani, T. Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish. Dev. Biol. 370, 71–85 (2012).Article

Shimizu，N.，Kawakami，K。＆Ishitani，T。使用高响应性Wnt/β-连环蛋白信号转导报告基因转基因斑马鱼可视化和探索Tcf/Lef功能。开发生物。370，71-85（2012）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Taipale, J. et al. Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nature 406, 1005–1009 (2000).Article

Taipale，J。等人。环巴胺可以逆转平滑和修补中致癌突变的影响。自然4061005-1009（2000）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Kinzler, K. W., Ruppert, J. M., Bigner, S. H. & Vogelstein, B. The GLI gene is a member of the Kruppel family of zinc finger proteins. Nature 332, 371–374 (1988).Article

Kinzler，K.W.，Ruppert，J.M.，Bigner，S.H。＆Vogelstein，B。GLI基因是锌指蛋白Kruppel家族的成员。自然332371-374（1988）。文章

ADS

PubMed

CAS

中科院

Google Scholar

谷歌学者

Zhang, Y. et al. Structural basis for cholesterol transport-like activity of the hedgehog receptor patched. Cell 175, 1352–1364.e14 (2018).Article

Zhang，Y.等人。修补的刺猬受体胆固醇转运样活性的结构基础。细胞1751352-1364.e14（2018）。文章

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Jia, S., Ren, Z., Li, X., Zheng, Y. & Meng, A. smad2 and smad3 are required for mesendoderm induction by transforming growth factor-beta/nodal signals in zebrafish. J. Biol. Chem. 283, 2418–2426 (2008).Article

Jia，S.，Ren，Z.，Li，X.，Zheng，Y。＆Meng，A。smad2和smad3是通过转化斑马鱼中的生长因子β/节点信号诱导中胚层所必需的。J、生物。化学。2832418-2426（2008）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Wang, F. et al. Structures of KIX domain of CBP in complex with two FOXO3a transactivation domains reveal promiscuity and plasticity in coactivator recruitment. Proc. Natl Acad. Sci. USA 109, 6078–6083 (2012).Article

与两个FOXO3a反式激活结构域复合的CBP KIX结构域的结构揭示了共激活因子募集中的滥交和可塑性。程序。国家科学院。科学。美国1096078–6083（2012）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Zhang, J. et al. Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage. Nat. Commun. 4, 2157 (2013).Article

Zhang，J.等人。使用由蛋白质切割激活的遗传编码荧光生物传感器可视化细胞中的半胱天冬酶-3样活性。国家公社。42157（2013）。文章

ADS

PubMed

Google Scholar

谷歌学者

Bindels, D. S. et al. mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Nat. Methods 14, 53–56 (2017).Article

Bindels，D.S.等人，mScarlet：一种用于细胞成像的明亮单体红色荧光蛋白。自然方法14,53-56（2017）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Yamamoto, K., Ichijo, H. & Korsmeyer, S. J. BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal protein kinase pathway normally activated at G 2 /M. Mol. Cell. Biol. 19, 8469–8478 (1999).Article

Yamamoto，K.，Ichijo，H。＆Korsmeyer，S.J。BCL-2被通常在G 2/M摩尔细胞中激活的ASK1/Jun N末端蛋白激酶途径磷酸化和失活。生物学198469-8478（1999）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Ansai, S. et al. Genome editing reveals fitness effects of a gene for sexual dichromatism in Sulawesian fishes. Nat. Commun. 12, 1350 (2021).Article

安塞（Ansai，S.）等人（Genome editing）揭示了苏拉威西鱼类中性二色性基因的适应性效应。国家公社。121350（2021）。文章

ADS

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Hwang, W. Y. et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat. Biotechnol. 31, 227–229 (2013).Article

Hwang，W.Y.等人。使用CRISPR-Cas系统在斑马鱼中进行有效的基因组编辑。美国国家生物技术公司。。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Kimura, Y., Hisano, Y., Kawahara, A. & Higashijima, S. Efficient generation of knock-in transgenic zebrafish carrying reporter/driver genes by CRISPR/Cas9-mediated genome engineering. Sci. Rep. 4, 6545 (2014).Article

Kimura，Y.，Hisano，Y.，Kawahara，A。＆Higashijima，S。通过CRISPR/Cas9介导的基因组工程有效生成携带报告基因/驱动基因的敲入转基因斑马鱼。Sci。代表46545（2014）。文章

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Kardash, E. Current Methods in Zebrafish Research. Mater. Methods 2, 109 (2012).Lee, Y. A., Cho, E. J. & Yokozawa, T. Protective Effect of Persimmon (Diospyros kaki) Peel Proanthocyanidin against Oxidative Damage under H2O2-Induced Cellular Senescence. Biol. Pharm. Bull. 31, 1265–1269 (2008).Article .

Kardash，E。斑马鱼研究的当前方法。马特。方法2109（2012）。Lee，Y.A.，Cho，E.J。和Yokozawa，T。柿子（柿子）皮原花青素对H2O2诱导的细胞衰老下氧化损伤的保护作用。生物制药公牛。311265-1269（2008）。文章。

PubMed

CAS

中科院

Google Scholar

谷歌学者

Thisse, C. & Thisse, B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat. Protoc. 3, 59–69 (2008).Article

Thisse，C。＆Thisse，B。与整个斑马鱼胚胎的高分辨率原位杂交。自然协议。3，59-69（2008）。文章

PubMed

CAS

中科院

Google Scholar

谷歌学者

Brend, T. & Holley, S. A. Zebrafish whole mount high-resolution double fluorescent in situ hybridization. J. Vis. Exp. JoVE 1229 https://doi.org/10.3791/1229. (2009)Tsuneoka, Y. & Funato, H. Modified in situ Hybridization Chain Reaction Using Short Hairpin DNAs. Front. Mol. Neurosci.

Brend，T。＆Holley，S.A。斑马鱼整装高分辨率双荧光原位杂交。J、可见。实验JoVE 1229https://doi.org/10.3791/1229.（2009）Tsuneoka，Y。＆Funato，H。使用短发夹DNA修饰原位杂交链式反应。正面。分子神经科学。

13, 75 (2020).Article .

13，75（2020）。文章。

PubMed

PubMed Central

公共医学中心

CAS

中科院

Google Scholar

谷歌学者

Prieto, C. & Barrios, D. RaNA-Seq: interactive RNA-Seq analysis from FASTQ files to functional analysis. Bioinformatics 36, 1955–1956 (2020).Article

Prieto，C。和Barrios，D。RaNA-Seq：从FASTQ文件到功能分析的交互式RNA-Seq分析。生物信息学361955-1956（2020）。文章

CAS

中科院

Google Scholar

谷歌学者

Behringer, R. Manipulating the Mouse Embryo: A Laboratory Manual. (Cold Spring Harbor Laboratory Press, 2014).Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).Article

。（冷泉港实验室出版社，2014）。Hao，Y.等人。多模式单细胞数据的综合分析。细胞1843573-3587.e29（2021）。文章

PubMed

PubMed Central

PubMed 中心

CAS

中科院

Google Scholar

谷歌学者

Download referencesAcknowledgementsWe thank K. Kawakami, P. Beachy, S. Ishii, B. Vogelstein, B. Li, D. Gadella, and S. Korsmeyer for providing plasmids, and D. Masui and Ishitani lab members for their helpful discussions, technical support, and fish maintenance. This research was supported by the Takeda Science Foundation (T.I.), SECOM Science and Technology Foundation (T.I.), KOSE Cosmetology Foundation (T.I.), Astellas Foundation for Research on Metabolic Disorders (2022A1209) (Y.A.), JST SPRING (K.M.), JSPS Fellows (24KJ16170) (K.M.), Grant-in-Aid for Transformative Research Areas(A) (21H05287) (T.I.) (21H05288) (H.S.), Scientific Research (B) (22H02820) (T.I.), Challenging Exploratory Research (23K18242) (T.I.), Scientific Research on Innovative Areas (22H04845) (Y.A.), and Early-Career Scientists (21K15085) (Y.A.), MEXT Promotion of Development of a Joint Usage/Research System Project: Coalition of Universities for Research Excellence (CURE) Program (JPMXP1323015484) (T.I.), and AMED-CREST (24gm2010001h0001) (T.I.).Author informationAuthor notesThese authors contributed equally: Kanako Matsumoto, Yuki Akieda.Authors and AffiliationsDepartment of Homeostatic Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanKanako Matsumoto, Yuki Akieda, Yukinari Haraoka & Tohru IshitaniDepartment of Biological Sciences, Graduate School of Science, Osaka University, Suita, Osaka, JapanKanako Matsumoto & Tohru IshitaniLaboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, JapanNaoki Hirono & Hiroshi SasakiCenter for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, JapanTohru IshitaniJapan Agency for Medical Research and Development - Core Researc.

下载参考文献致谢我们感谢K.Kawakami，P.Beachy，S.Ishii，B.Vogelstein，B.Li，D.Gadella和S.Korsmeyer提供质粒，以及D.Masui和Ishitani实验室成员的有益讨论，技术支持和鱼类维护。这项研究得到了武田科学基金会（T.I.）、SECOM科学技术基金会（T.I.）、KOSE美容基金会（T.I.）、Astellas代谢紊乱研究基金会（2022A1209）（Y.A.）、JST SPRING（K.M.）、JSPS研究员（24KJ16170）（K.M.）、转化研究领域资助（A）（21H05287）（T.I.）（21H05288）（H.S.）、科学研究（B）（22H02820）（T.I.）、挑战性探索性研究（23K18242）（T.I.）、创新领域科学研究（22H04845）（Y.A.）和早期职业科学家（21K15085）（Y.A.），MEXT促进联合使用/研究系统项目的发展：卓越研究大学联盟（CURE）计划（JPMXP1323015484）（T.I.）和AMED-CREST（24gm2010001h0001）（T.I.）。作者信息作者注意到这些作者做出了同样的贡献：松本金子，秋田由纪。作者和附属机构大阪大学微生物疾病研究所稳态调节系，大阪，日本松本幸男，秋田幸男，原冈幸男和石田东郎生物科学系，大阪大学科学研究生院，大阪，日本松本幸男和石田东郎胚胎发生实验室，大阪大学前沿生物科学研究生院，大阪，大阪，日本广野和大阪大学传染病教育与研究中心（CiDER），大阪，大阪u IshitaniJapan医学研究与发展机构-核心研究中心。

PubMed Google ScholarYuki AkiedaView author publicationsYou can also search for this author in

PubMed Google ScholarYuki AkiedaView作者出版物您也可以在

PubMed Google ScholarYukinari HaraokaView author publicationsYou can also search for this author in

PubMed Google ScholarYukinari HaraokaView作者出版物您也可以在

PubMed Google ScholarNaoki HironoView author publicationsYou can also search for this author in

PubMed Google ScholarNaoki HironoView作者出版物您也可以在

PubMed Google ScholarHiroshi SasakiView author publicationsYou can also search for this author in

PubMed Google ScholarHiroshi SasakiView作者出版物您也可以在

PubMed Google ScholarTohru IshitaniView author publicationsYou can also search for this author in

PubMed Google ScholarTohru IshitaniView作者出版物您也可以在

PubMed Google ScholarContributionsConception and design: K.M., Y.A., T.I. wrote the main manuscript text; K.M., Y.A., T.I. analysed the data; K.M., Y.A., Y.H., N.H., H.S., T.I. prepared the figures. All authors have reviewed the manuscript.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献概念与设计：K.M.，Y.A.，T.I.撰写了主要手稿文本；K、 M.，Y.A.，T.I.分析了数据；K、 M.，Y.A.，Y.H.，N.H.，H.S.，T.I.准备了这些数字。所有作者都审阅了手稿。对应作者对应。

Tohru Ishitani.Ethics declarations

石谷东鲁。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Peer review

同行评审

Peer review information

同行评审信息

Nature Communications thanks Jungmin Choi, Miguel Torres and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Nature Communications感谢Jungmin Choi，Miguel Torres和另一位匿名审稿人对这项工作的同行评审所做的贡献。可以获得同行评审文件。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary InformationDescription of Additional Supplementary FilesSupplementary Movie 1Supplementary Movie 2Supplementary Movie 3Reporting SummaryTransparent Peer Review fileSource dataSource DataRights and permissions.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息其他补充文件的描述补充电影1补充电影2补充电影3报告摘要透明同行评审文件源数据源数据权限。

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleMatsumoto, K., Akieda, Y., Haraoka, Y. et al. Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development.

转载和许可本文引用本文Matsumoto，K.，Akieda，Y.，Haraoka，Y。等人。Foxo3介导的生理细胞竞争确保了整个脊椎动物发育过程中强大的组织模式。

Nat Commun 15, 10662 (2024). https://doi.org/10.1038/s41467-024-55108-xDownload citationReceived: 31 October 2023Accepted: 27 November 2024Published: 17 December 2024DOI: https://doi.org/10.1038/s41467-024-55108-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Nat Commun 1510662（2024）。https://doi.org/10.1038/s41467-024-55108-xDownload收到引文日期：2023年10月31日接受日期：2024年11月27日发布日期：2024年12月17日OI：https://doi.org/10.1038/s41467-024-55108-xShare。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

Subjects

主题

ApoptosisBody patterningDevelopmental neurogenesisMusculoskeletal development

细胞凋亡身体模式发育神经发生肌肉骨骼发育

全球产业链接平台

重庆市渝北区金星科技大厦A区5楼512室

联系电话：023-67139735（重庆）

关于我们

联系我们

加入我们