成人下丘脑被细分为不同的领域:视前,前,结节和乳头。每个域都包含一系列神经元,这些神经元共同作用以调节稳态。下丘脑神经元的胚胎起源和发育,然而,仍然神秘。这里,我们总结了模型生物的最新研究,这些研究挑战了下丘脑发育的当前观点,传统上试图将成人结构域映射到相应定位的胚胎结构域。相反,新的研究表明,下丘脑神经元来自经历各向异性生长的祖细胞,扩张到比其他祖细胞更大的程度,在不同的维度上成长。我们特别描述了表达Shh/Fgf10的多能祖细胞群体如何在整个下丘脑的基底中产生各向异性和顺序生长的祖细胞:首先,头端移位的子集产生前腹/结节神经元祖细胞;然后尾端移位的子集产生乳头神经元祖细胞;并且,最后,腹侧移位的子集产生结节漏斗胶质祖细胞。当这种情况发生时,Shh+ive和Fgf10+ive祖细胞的稳定种群形成。我们描述了目前对诱导Shh+ive/Fgf10+ive祖细胞并开始将其分化为前腹/结节神经元祖细胞的机制的理解,乳头神经元祖细胞和结节漏斗祖细胞。一起来看,这些研究提出了一种下丘脑发育的新模型,我们称之为“各向异性生长模型”。我们讨论了该模型对理解成人下丘脑神经元起源的意义。
The adult hypothalamus is subdivided into distinct domains: pre-optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh/ Fgf10-expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior-ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh+ive and Fgf10+ive progenitors form. We describe current understanding of the mechanisms that induce Shh+ive /Fgf10+ive progenitors and begin to direct their differentiation to anterior-ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the \"anisotropic growth model\". We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.