Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Inserm UMR-S1172, F-59000 Lille, France.
J Chem Neuroanat. 2022 Sep;123:102117. doi: 10.1016/j.jchemneu.2022.102117. Epub 2022 Jun 6.
The hypothalamus is a large brain region made of nuclei and areas involved in the control of behaviors and physiological regulations. Among them, the arcuate nucleus (ARH) and the lateral hypothalamic area (LHA) contain key neuronal populations expressing the pro-opiomelanocortin (POMC), the agouti-related peptide (AgRP), and the melanin-concentrating hormone (MCH), respectively, that are involved in goal-oriented behaviors (such as feeding behavior) and glucose homeostasis. These neuronal populations are generated from distinct parts of the germinative neuroepithelium during embryonic life, and acquire their cell fate under the influence of morphogen proteins, specific transcription factors, and epigenetic modulators. POMC and MCH neuronal development continues by sending long descending axonal projections before birth under the control of axon guidance molecules such as Netrin1 and Slit2. Later, during the postnatal period, POMC and AgRP neurons develop intra-hypothalamic projections notably to the paraventricular nucleus of the hypothalamus through the influence of other axon guidance cues such as the class3 Semaphorins. Other cellular processes, such as autophagy and primary cilia function, and hormonal cues also appear critical for the proper development of POMC neurons.
下丘脑是一个由核和区域组成的大脑区域，涉及行为和生理调节的控制。其中，弓状核（ARH）和外侧下丘脑区域（LHA）分别包含表达前阿黑皮素原（POMC）、刺鼠相关肽（AgRP）和黑色素浓缩激素（MCH）的关键神经元群体，这些神经元群体参与目标导向行为（如进食行为）和葡萄糖稳态。这些神经元群体是在胚胎生命期间从生殖神经上皮的不同部位产生的，并在形态发生蛋白、特定转录因子和表观遗传调节剂的影响下获得其细胞命运。POMC 和 MCH 神经元的发育在出生前通过 Netrin1 和 Slit2 等轴突导向分子的控制下，发送长的下行轴突投射继续进行。之后，在出生后期间，POMC 和 AgRP 神经元通过其他轴突导向线索（如 Semaphorin 类 3）的影响，在大脑下部分别发育出向下丘脑室旁核的内下丘脑投射。其他细胞过程，如自噬和初级纤毛功能以及激素线索，也似乎对 POMC 神经元的正常发育至关重要。
