A genetic analysis of hypothalamic development and function using Ptf1a-genetically modified mice.

Ptf1a是一种bHLH转录因子，在哺乳动物胰腺的发育过程中起着至关重要的作用。几个小组和我们已经报道了Ptf1a参与了中枢神经系统区域的神经元亚型规范。在这里，我们报道了Ptf1a在发育中的下丘脑中的表达。下丘脑参与了动态平衡的调节；然而，下丘脑神经元的发育机制和功能仍有待了解。在发育过程中，我们发现Ptf1a表达于间脑神经上皮的一部分，即下丘脑神经元的来源。利用Cre/loxP系统，我们在下丘脑腹侧核内发现了许多“Ptf1a系细胞”。在发育中的下丘脑中，该基因的条件性敲除(CKO)导致活动减少导致的迟发性肥胖和不孕不育。这些结果表明，间脑中的Ptf1a对下丘脑神经元的正常发育和包括体重在内的代谢控制是必需的。

Ptf1a, a bHLH-transcription factor, is known to be essential for the development of mammalian pancreas. Several groups and we have reported involvement of Ptf1a in neuron subtype specification in CNS regions. Here we report Ptf1a expression in the developing hypothalamus.Hypothalamus is involved in the regulation of homeostasis; however, developmental mechanism and function of hypothalamic neurons remain to be understood. During development, we found Ptf1a was expressed in a part of diencephalic neuroepithelium, that is, a source of hypothalamic neurons. Using the Cre/loxP system, we identified many "Ptf1a lineage cells" in the several ventral hypothalamic nucleus. Conditional knockout (cKO) of this gene in the developing hypothalamus resulted in late-onset obesity caused by lower activity, and infertility. The present results suggest that Ptf1a in diencephalon is required for the normal development of function of hypothalamic neurons and the metabolic control, including body weight.