Interaction of Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis

被引:91
作者
Archer, Tenley C. [1 ]
Jin, Jing [1 ]
Casey, Elena S. [1 ]
机构
[1] Georgetown Univ, Dept Biol, Washington, DC 20057 USA
关键词
Sox; Neural progenitor; Bicistronic; 2A; Oct4/Pou91; LINKED MENTAL-RETARDATION; AUTOSOMAL SEX REVERSAL; TRANSCRIPTIONAL ACTIVATION; CAMPOMELIC DYSPLASIA; XENOPUS EMBRYOS; NEURAL TISSUE; STEM-CELLS; EXPRESSION; GENE; IDENTIFICATION;
D O I
10.1016/j.ydbio.2010.12.013
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sox1, Sox2 and Sox3, the three members of the SoxB1 subgroup of transcription factors, have similar sequences, expression patterns and overexpression phenotypes. Thus, it has been suggested that they have redundant roles in the maintenance of neural stem cells in development. However, the long-term effect of overexpression or their function in combination with their putative co-factor Oct4 has not been tested. Here, we show that overexpression of sox1, sox2, sox3 or oct91, the Xenopus homologue of Oct4, results in the same phenotype: an expanded neural plate at the expense of epidermis and delayed neurogenesis. However, each of these proteins induced a unique profile of neural markers and the combination of Oct91 with each SoxB1 protein had different effects, as did continuous misexpression of the proteins. Overexpression studies indicate that Oct91 preferentially cooperates with Sox2 to maintain neural progenitor marker expression, while knockdown of Oct91 inhibits neural induction driven by either Sox2 or Sox3. Continuous expression of Sox1 and Sox2 in transgenic embryos represses neuron differentiation and inhibits anterior development while increasing cell proliferation. Constitutively active Sox3, however, leads to increased apoptosis suggesting that it functions as a tumor suppressor. While the SoxB1s have overlapping functions, they are not strictly redundant as they induce different sets of genes and are likely to partner with different proteins to maintain progenitor identity. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:429 / 440
页数:12
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