Hedgehog signaling is involved in development of the neocortex
Hedgehog signaling is involved in development of the neocortex
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DOI：
10.1242/dev.015891
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发表时间：
2008-08-15
期刊：
影响因子：
4.6
通讯作者：
Ishibashi, Makoto
中科院分区：
文献类型：
--
作者：
Komada, Munekazu;Saitsu, Hirotomo;Ishibashi, Makoto
Sonic hedgehog（Shh）功能对于图案化和细胞命运规范是必不可少的，特别是在中枢神经系统的腹侧区域。它也是小脑颗粒神经元前体细胞的重要有丝分裂原，在维持出生后端脑干细胞生态位中起重要作用。虽然据报道，Shh在发育中的端脑背侧表达，但Shh在该区域的功能尚不清楚，Shh mRNA转录物原位的详细表征尚未得到证实。为了阐明Shh信号在背侧软腭（新皮层原基）发育中的作用，我们使用Emx 1（cre）小鼠特异性地敲除了端脑背侧发育早期的Shh和Smo基因。突变体在E18.5时显示出较小的端脑背侧，这是由神经祖细胞/干细胞的细胞周期动力学缺陷引起的。祖细胞/干细胞的细胞周期延长，退出周期的细胞数量减少，神经发生减少。出生日期分析显示突变体的神经元位置异常.室管膜下区、室管膜区和亚板细胞的特征也受到影响。野生型端脑背侧检测到Shh的弱免疫反应性。突变体端脑背侧的Shh免疫反应性降低支持上述表型。我们的数据表明Shh信号在新皮质的发育中发挥着重要作用。
Sonic hedgehog (Shh) function is essential for patterning and cell fate specification, particularly in ventral regions of the central nervous system. It is also a crucial mitogen for cerebellar granule neuron precursors and is important in maintenance of the stem cell niche in the postnatal telencephalon. Although it has been reported that Shh is expressed in the developing dorsal telencephalon, functions of Shh in this region are unclear, and detailed characterization of Shh mRNA transcripts in situ has not been demonstrated. To clarify the roles of Shh signaling in dorsal pallium ( neocortex primordium) development, we have knocked out the Shh and Smo genes specifically in the early developing dorsal telencephalon by using Emx1(cre) mice. The mutants showed a smaller dorsal telencephalon at E18.5, which was caused by cell cycle kinetics defects of the neural progenitor/stem cells. The cell cycle length of the progenitor/stem cells was prolonged, and the number of cycle-exiting cells and neurogenesis were decreased. Birth- date analysis revealed abnormal positioning of neurons in the mutants. The characteristics of the subventricular zone, ventricular zone and subplate cells were also affected. Weak immunoreactivity of Shh was detected in the dorsal telencephalon of wild types. Reduced Shh immunoreactivity in mutant dorsal telencephalons supports the above phenotypes. Our data indicate that Shh signaling plays an important role in development of the neocortex.