Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene
Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene
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DOI：
10.1101/gad.13.21.2787
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发表时间：
1999-11-01
影响因子：
10.5
通讯作者：
Simeone, A
中科院分区：
文献类型：
--
作者：
Acampora, D;Postiglione, MP;Simeone, A
神经内分泌下丘脑的发育以一系列精确的形态发生里程碑为特征，最终导致神经分泌细胞谱系的终末分化。同源盒基因Orthopedia(OTP)在神经元中表达，在发育过程中形成室旁核(PVN)、视上核(SON)、脑室周前核(APV)和弓状核(ARN)。OTP(-/-)纯合子小鼠出生后不久死亡，并表现出关键的神经内分泌发育事件的进行性损害，如细胞增殖减少，细胞异常迁移，以及APV、PVN、SON和ARN的小细胞和大细胞神经元的终末分化失败。此外，我们的数据提供了证据，OTP和SIM1，一种bHLH-PAS转录因子，指导PVN，SON和APV的末端分化，平行地起作用，都是维持Brn2表达所必需的，而Brn2是分泌催产素(OT)、精氨酸加压素(AVP)和促肾上腺皮质激素释放激素(CRH)的神经细胞所必需的。
Development of the neuroendocrine hypothalamus is characterized by a precise series of morphogenetic milestones culminating in terminal differentiation of neurosecretory cell lineages. The homeobox-containing gene Orthopedia (Otp) is expressed in neurons giving rise to the paraventricular (PVN), supraoptic (SON), anterior periventricular (aPV), and arcuate (ARN) nuclei throughout their development. Homozygous Otp(-/-) mice die soon after birth and display progressive impairment of crucial neuroendocrine developmental events such as reduced cell proliferation, abnormal cell migration, and failure in terminal differentiation of the parvocellular and magnocellular neurons of the aPV, PVN, SON, and ARN. Moreover, our data provide evidence that Otp and Sim1, a bHLH-PAS transcription factor that directs terminal differentiation of the PVN, SON, and aPV, act in parallel and are both required to maintain Brn2 expression which, in turn, is required for neuronal cell lineages secreting oxytocin (OT), arginine vasopressin (AVP), and corticotropin-releasing hormone (CRH).