Antagonizing activity of chick Grg4 against tectum-organizing activity.
Antagonizing activity of chick Grg4 against tectum-organizing activity.
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雏鸡 Grg4 对抗顶盖组织活性的拮抗活性。
DOI：
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发表时间：
2000
影响因子：
2.7
通讯作者：
Harukazu Nakamura
中科院分区：
文献类型：
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作者：
S. Sugiyama;J. Funahashi;Harukazu Nakamura
鸡中脑的翼板分化为视顶盖。它已被证明，在mes-metencephalic边界表达的因素诱导顶盖，并给出位置特异性。鸡Grg 4首先在前神经褶中表达。到第10期，表达从后间脑定位到中脑。为了研究Grg 4在中脑发育中的功能，通过卵内电穿孔进行Grg 4过表达。在Grg 4过表达后，En-2、Pax 5、Fgf 8和EphrinA 2的表达被抑制，并且Pax 6在中脑区域被上调。GRG 4过表达引起形态学改变，中脑肿胀变小，中脑间界后移，即顶盖的前界后移。重要的是，Grg 4与Pax 5共转染取消了Pax 5的顶盖诱导活性。这些结果表明，Grg 4作为一个拮抗剂对顶盖组织活动。转染Grg 4的N端结构域诱导En-2表达。由于N-末端结构域被转运到神经上皮细胞的细胞核中，它们可以作为内源性Grg 4的显性阴性。这些结果表明，Grg 4对组织分子具有抑制作用，并提示Grg 4在顶盖前界和极性的形成中起重要作用。
Alar plate of chick mesencephalon differentiates into the optic tectum. It has been shown that factors expressed in the mes-metencephalic boundary induce the tectum and give positional specificity. Chick Grg4 is expressed at first in the anterior neural fold. The expression localizes from the posterior diencephalon to the mesencephalon by stage 10. To investigate the function of Grg4 in mesencephalic development, Grg4 overexpression was carried out by in ovo electroporation. After Grg4 overexpression, expression of En-2, Pax5, Fgf8, and EphrinA2 was repressed, and Pax6 was upregulated in the mesencephalic region. Grg4 overexpression caused the morphological change; mesencephalic swelling became smaller and the di-mesencephalic boundary shifted posteriorly, that is, the anterior limit of tectum shifted posteriorly. Importantly, cotransfection of Grg4 with Pax5 canceled the tectum-inducing activity of Pax5. These results suggest that Grg4 works as an antagonist against tectum-organizing activity. It was also shown that transfected N-terminal domains of Grg4 induced En-2 expression. Since N-terminal domains were transported to the nucleus in the neuroepithelium, they could act as dominant negative for endogenous Grg4. These results indicate that Grg4 has repressing activity against the organizing molecules and suggest that Grg4 plays important roles in formation of anterior tectal boundary and polarity.