AbstractThe tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. In this Review, we explore the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes.

摘要下丘脑结节调节一系列关键的生理过程，包括能量稳态和代谢。在这篇综述中，我们探讨了控制下丘脑结节发育的复杂分子机制和信号通路，重点关注影响代谢结果的方面。

Major developmental events are discussed in the context of their effect on the establishment of both functional hypothalamic neuronal circuits and brain–body interfaces that are pivotal to the control of metabolism. Emerging evidence indicates that aberrations in molecular pathways during tuberal hypothalamic development contribute to metabolic dysregulation.

讨论了主要的发育事件对建立功能性下丘脑神经元回路和对代谢控制至关重要的脑-体界面的影响。新出现的证据表明，下丘脑结节发育过程中分子途径的异常会导致代谢失调。

Understanding the molecular underpinnings of tuberal hypothalamic development provides a comprehensive view of neurodevelopmental processes and offers a promising avenue for future targeted interventions to prevent and treat metabolic disorders.Key points.

了解结节性下丘脑发育的分子基础，可以全面了解神经发育过程，并为未来预防和治疗代谢紊乱的有针对性的干预措施提供了有希望的途径。关键点。

Energy balance is regulated by pro-opiomelanocortin and neuropeptide Y neurons within the arcuate nucleus and by tanycytes within the median eminence.

能量平衡受弓状核内的前黑素皮质素和神经肽Y神经元以及正中隆起内的tanycytes调节。

Sequential signalling events govern the progression of diencephalic prethalamic-like cells to generate regionally distinct populations of hypothalamic progenitors; sustained signalling events and hierarchical transcription factor networks mediate tuberal neurogenesis and the specification of tuberal neuronal subtypes and tanycytes..

顺序信号事件控制间脑丘脑前样细胞的进展，以产生区域不同的下丘脑祖细胞群；持续的信号传导事件和分级转录因子网络介导结节神经发生以及结节神经元亚型和tanycytes的规范。。

Leptin and a high-fat diet regulate diverse aspects of tuberal cell specification, including neurogenesis, axon guidance and synaptic connectivity.

瘦素和高脂肪饮食调节结节细胞规格的各个方面，包括神经发生，轴突导向和突触连接。

Neurons of the tuberal hypothalamus are sexually dimorphic in their distribution and regulate sexually dimorphic patterns of behaviour.

。

Genetic and environmental factors disrupt tuberal hypothalamic development and lead to lifelong metabolic defects.

遗传和环境因素破坏了结节下丘脑的发育并导致终身代谢缺陷。

Directed differentiation of human induced pluripotent stem cells towards hypothalamic identities is in its infancy but holds the promise of generating therapeutically important tuberal hypothalamic cell types.

人类诱导的多能干细胞向下丘脑身份的定向分化尚处于起步阶段，但有望产生治疗上重要的结节性下丘脑细胞类型。

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Fig. 1: Anatomy of the adult and developing tuberal hypothalamus.Fig. 2: Gene regulatory networks underlying HypFP and tuberal progenitor specification.Fig. 3: Topology of the hypothalamus at neurogenic stages.Fig. 4: Molecular pathways underlying ARCN neuronal and tuberal tanycyte differentiation.Fig.

图1：成人和发育中的下丘脑结节的解剖结构。。图3：神经源性阶段下丘脑的拓扑结构。图4:ARCN神经元和结节tanycyte分化的分子途径。图。

5: Stage-specific insults to the developing hypothalamus and their role in metabolic disorders..

5： 对发育中的下丘脑的阶段性侮辱及其在代谢紊乱中的作用。。

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Download referencesAcknowledgementsThis work was supported by the Wellcome Trust (212247/Z/18/Z) to M.P., the NIH (R01MH126676) to S.B. and the Lundbeckfonden grant (R361-2020-2654) to D.W.K.Author informationAuthors and AffiliationsSchool of Biosciences, University of Sheffield, Sheffield, UKMarysia Placzek & Kavitha ChinnaiyaBateson Centre, University of Sheffield, Sheffield, UKMarysia PlaczekNeuroscience Institute, University of Sheffield, Sheffield, UKMarysia PlaczekDanish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, DenmarkDong Won KimDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDong Won KimSolomon H.

。

Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USASeth BlackshawDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USASeth BlackshawDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USASeth BlackshawInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USASeth BlackshawKavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USASeth BlackshawAuthorsMarysia PlaczekView author publicationsYou can also search for this author in.

约翰·霍普金斯大学医学院神经科学系，马里兰州巴尔的摩，USASeth Blackshaw，约翰·霍普金斯大学医学院眼科，巴尔的摩，马里兰州，USASeth Blackshaw，约翰·霍普金斯大学医学院神经病学系，巴尔的摩，马里兰州，USASeth BlackshawInstitute for Cell Engineering，约翰·霍普金斯大学医学院，巴尔的摩，马里兰州，USASeth BlackshawKavli Neuroscience Discovery Institute，约翰·霍普金斯大学医学院，巴尔的摩，USASeth BlackshawAuthorsMarysia PlaczekView author Publications你也可以在中搜索这位作者。（笑声）。

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Nature Reviews Endocrinology thanks Karine Rizzoti, Julie Chowen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

《自然评论》内分泌学感谢Karine Rizzoti，Julie Chowen和另一位匿名审稿人对这项工作的同行评审做出的贡献。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Rights and permissionsReprints and permissionsAbout this articleCite this articlePlaczek, M., Chinnaiya, K., Kim, D.W. et al. Control of tuberal hypothalamic development and its implications in metabolic disorders..

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。权利和许可打印和许可本文引用本文Placzek，M.，Chinnaiya，K.，Kim，D.W.等人控制下丘脑结节发育及其对代谢紊乱的影响。。

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