Sanz Elisenda, Quintana Albert, Deem Jennifer D, Steiner Robert A, Palmiter Richard D, McKnight G Stanley
Department of Pharmacology, Center for Integrative Brain Research and Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington 98101.
Department of Biochemistry, Howard Hughes Medical Institute, Center for Integrative Brain Research and Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington 98101.
J Neurosci. 2015 Apr 8;35(14):5549-56. doi: 10.1523/JNEUROSCI.3614-14.2015.
Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. We developed a novel approach to examine the developmental pathways that link specific subtypes of neurons by combining embryonic and adult ribosome-tagging strategies in mice. This new method shows that Pomc-expressing precursors not only differentiate into discrete neuronal populations that mediate energy balance (POMC and AgRP neurons), but also into neurons critical for puberty onset and the regulation of reproductive function (Kiss1 neurons). These results demonstrate a developmental link between nutrient-sensing and reproductive neuropeptide synthesizing neuronal populations and suggest a potential pathway that could link maternal nutrition to reproductive development in the offspring.
下丘脑神经元群体是能量平衡和生殖功能的核心调节者。然而，这些关键下丘脑神经元群体的个体发育过程很大程度上仍不清楚。我们开发了一种新方法，通过结合小鼠胚胎和成年期的核糖体标记策略，来研究连接特定神经元亚型的发育途径。这种新方法表明，表达阿黑皮素原（Pomc）的前体细胞不仅分化为介导能量平衡的离散神经元群体（POMC和AgRP神经元），还分化为对青春期启动和生殖功能调节至关重要的神经元（Kiss1神经元）。这些结果证明了营养感知神经元群体与生殖神经肽合成神经元群体之间的发育联系，并提示了一条可能将母体营养与后代生殖发育联系起来的潜在途径。
