The arcuate nucleus of the hypothalamus is central in the regulation of body weight homeostasis through its ability to sense peripheral metabolic signals and relay them, through neural circuits, to other brain areas, ultimately affecting physiological and behavioural changes. The early postnatal development of these neural circuits is critical for normal body weight homeostasis, such that perturbations during this critical period can lead to obesity. The role for peripheral regulators of body weight homeostasis, including leptin, insulin and ghrelin, in this postnatal development is well described, yet some of the fundamental processes underpinning axonal and dendritic growth remain unclear. Here, we hypothesised that molecules known to regulate axonal and dendritic growth processes in other areas of the developing brain would be expressed in the postnatal arcuate nucleus and/or target nuclei where they would function to mediate the development of this circuitry. Using state-of-the-art RNAscope^® technology, we have revealed the expression patterns of genes encoding Dcc/Netrin-1, Robo1/Slit1 and Fzd5/Wnt5a receptor/ligand pairs in the early postnatal mouse hypothalamus. We found that individual genes had unique expression patterns across developmental time in the arcuate nucleus, paraventricular nucleus of the hypothalamus, ventromedial nucleus of the hypothalamus, dorsomedial nucleus of the hypothalamus, median eminence and, somewhat unexpectedly, the third ventricle epithelium. These observations indicate a number of new molecular players in the development of neural circuits regulating body weight homeostasis, as well as novel molecular markers of tanycyte heterogeneity.

中文翻译：

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控制神经回路形成的发育基因在出生后早期的下丘脑和第三脑室的细胞内膜中表达

下丘脑弓状核通过其感知外周代谢信号并通过神经回路将它们传递到其他大脑区域的能力，在调节体重稳态中处于中心地位，最终影响生理和行为变化。这些神经回路的早期出生后发育对于正常体重稳态至关重要，因此在这个关键时期的扰动会导致肥胖。体重稳态的外周调节因子（包括瘦素、胰岛素和生长素释放肽）在这种出生后发育中的作用已得到很好的描述，但一些支撑轴突和树突生长的基本过程仍不清楚。这里，我们假设已知在发育中大脑的其他区域调节轴突和树突生长过程的分子将在出生后弓状核和/或靶核中表达，在那里它们将发挥作用以介导该电路的发育。使用最先进的 RNAscope^®技术，我们揭示了编码 Dcc/Netrin-1、Robo1/Slit1 和 Fzd5/Wnt5a 受体/配体对的基因在出生后早期小鼠下丘脑中的表达模式。我们发现，个体基因在弓状核、下丘脑室旁核、下丘脑腹内侧核、下丘脑背内侧核、正中隆突和第三脑室上皮细胞的发育过程中具有独特的表达模式。这些观察结果表明，在调节体重稳态的神经回路的发展中，许多新的分子参与者，以及新的 tanycyte 异质性分子标志物。