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

Ptf1a 是一种 bHLH 转录因子，已知对哺乳动物胰腺的发育至关重要。几个小组和我们已经报道了 Ptf1a 参与 CNS 区域神经元亚型规范的情况。在这里，我们报告了发育中的下丘脑中 Ptf1a 的表达。下丘脑参与体内平衡的调节；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在间脑神经上皮的一部分（即下丘脑神经元的来源）中表达。使用 Cre/loxP 系统，我们在几个下丘脑腹侧核中鉴定了许多“Ptf1a 谱系细胞”。发育中的下丘脑中该基因的条件性敲除（cKO）会导致由于活动降低而导致迟发性肥胖和不育。目前的结果表明，间脑中的 Ptf1a 是下丘脑神经元功能正常发育和代谢控制（包括体重）所必需的。

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.