Gli/Zic factors pattern the neural plate by defining domains of cell differentiation

Gli/Zic factors pattern the neural plate by defining domains of cell differentiation
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DOI:
10.1038/31242
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发表时间:
1998-06-11
期刊:
影响因子:
64.8
通讯作者:
Altaba, ARI
Altaba, ARI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brewster, R;Lee, J;Altaba, ARI

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早期蛙神经板分化出三种细胞类型:外侧边缘的神经嵴、中线的底板和两侧三条带的初级神经元。声刺猬(1,2)(Shh)和神经嵴和背侧诱导底板细胞和腹侧神经元。神经元由表皮因子如骨形态发生蛋白(BMP)诱导(3)。条纹内细胞亚群中的神经发生涉及侧抑制(4)。然而,池的前体被定义在定型域中响应于诱导信号的过程是未知的。在这里,我们表明,青蛙Zic 2编码的锌指转录因子的Gli超家族,这是在条纹中表达的交替与那些在其中的初级神经元分化和重叠的域的底板和神经嵴祖细胞。Zic 2抑制神经发生并诱导神经嵴分化。相反,Gli蛋白广泛表达,诱导神经发生并抑制神经嵴分化。因此,Zic 2是脊椎动物前模式基因,编码抗神经源性和嵴诱导功能,其抵消Gli蛋白的神经源性活性而不是底板诱导活性。我们提出Gli/Zic基因的组合功能响应于诱导信号并诱导图案化的神经细胞分化。
Three cell types differentiate in the early frog neural plate: neural crest at the lateral edges, floorplate at the midline and primary neurons in three bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic hedgehog(1,2) (Shh) and neural crest and dorsal. neurons are induced by epidermal factors such as bone morphogenetic proteins (BMPs)(3). Neurogenesis in a subset of cells within the stripes involves lateral inhibition(4). However, the process by which pools of precursors are defined in stereotypic domains in response to inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger transcription factor of the Gli superfamily which is expressed in stripes that alternate with those in which primary neurons differentiate and overlap the domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis and induces neural crest differentiation. Conversely, Gli proteins are widely expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest-inducing functions that counteract the neurogenic but not the floorplate-inducing activity of Gli proteins. We propose that the combined function of Gli/Zic genes responds to inductive signals and induces patterned neural cell differentiation.