Retinal Patterning by Pax6-Dependent Cell Adhesion Molecules
Retinal Patterning by Pax6-Dependent Cell Adhesion Molecules
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DOI：
10.1002/dneu.20816
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发表时间：
2010-09-15
影响因子：
3
通讯作者：
Rungger, Duri
中科院分区：
文献类型：
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作者：
Rungger-Braendle, Elisabeth;Ripperger, Juergen A.;Rungger, Duri
从Pax6突变胚胎中获得的长期证据表明，依赖于Pax6的细胞黏附分子参与了中枢神经系统，特别是视网膜的模式形成。然而，这种途径的直接证据仍然难以捉摸。我们提供的直接证据表明，在非洲爪哇胚胎中，吗啡反义分子下调Pax6的表达，以及母体N-钙粘附素(MNcad)、N-钙粘附素(Ncad)和神经细胞黏附分子(NCAM)的下调可以产生类似的表型。眼球形成减少，视网膜板层严重紊乱。在Pax6基因敲除胚胎中，编码这些细胞黏附分子的mRNAs水平显著降低。过表达Pax6可以有效地挽救Pax6基因敲除胚胎的表型，并恢复这些可能的靶基因的表达。通过假定的靶基因mNcad挽救Pax6缺乏症可以适度挽救眼睛的形成。根据计算机分析，编码细胞黏附分子的基因的启动子包含几个假定的Pax6结合位点。染色质免疫沉淀显示，在胚胎头部，Pax6结合到包含这些预测结合位点的启动子区域。因此，几个细胞黏附分子是Pax6的直接靶基因，并在视网膜图案形成中协同作用。(C)2010 Wiley期刊，Inc.开发神经生物学70：764-780,2010
Long-standing evidence gained from Pax6 mutant embryos pointed to an involvement of Pax6-dependent cell adhesion molecules in patterning the central nervous system and, in particular, the retina. However, direct evidence for such pathways remained elusive. We here present direct evidence that knockdown of Pax6 expression by morpholino antisense molecules in Xenopus embryos and knockdown of maternal N-cadherin (mNcad), N-cadherin (Ncad) and neural cell adhesion molecule (NCAM) produce similar phenotypes. Eye formation is reduced and retinal lamination is heavily disorganized. In Pax6 knockdown embryos, the levels of mRNAs coding for these cell adhesion molecules are markedly reduced. Overexpression of Pax6 efficiently rescues the phenotype of Pax6 knockdown embryos and restores expression of these putative target genes. Rescue of Pax6-deficiency by the putative target gene mNcad moderately rescues eye formation. The promoters of the genes coding for cell adhesion molecules contain several putative Pax6 binding sites, as determined by computer analysis. Chromatin immunoprecipitation shows that, in embryonic heads, Pax6 binds to promoter regions containing such predicted binding sites. Thus, several cell adhesion molecules are direct target genes of Pax6 and cooperate in retinal patterning. (C) 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 764-780, 2010