The expression patterns of Cdc25A, Cdc25B, Sox2 and Mnb in central nervous system in early chicken embryos

Asian - Australasian Journal of Animal Sciences, June, 2009 by Hui Zhang, Junhui Qin, Jingjing Cao, Nainan Hei, Chunsheng Xu, Ping Yang, Haili Liu, Xiaohong Chu, Huijun Bao, Qiusheng Chen

Recent evidence suggests that all three isoforms can dephosphorylate Cdc2/cyclin B and play important roles in the G1/S and G2/M transitions of the cell cycle (Mailand et al., 2002; Perry and Kornbluth, 2007). Expression patterns of Cdc25A and Cdc25B were complementary in HH stage 10 in chick embryo CNS. When one Cdc25 is inhibited or deactivated, the other will be activated and replace it. Both Cdc25 phosphatases seem to function as key regulators of the G1-S and G2-M transitions and of mitosis, to spatially and temporally regulate their respective CDK substrates. The two Cdc25 phosphatases appear to cooperate during each stage of the cell cycle to activate the relevant CDK/cyclin complexes. A single Cdc25 protein that possesses characteristics of multiple Cdc25 isoforms, is capable of performing all phosphatase-dependent activation of CDK/cyclin complexes required for normal cell division (Russell et al., 1986). Cdc25A and Cdc25B may possess functional redundancy to regulate cell proliferation in CNS development. However, expression patterns of Cdc25A and Cdc25B are differential, for example, in somites, indicating that perhaps the redundancy between the different Cdc25 isoforms is limited. Functional redundancy is a universal feature of cell cycle regulators that have evolved from common ancestors to fulfill more specialised functions, but that have kept the ability to carry on most of the functions of the other family members (Boutros et al., 2006).

Cdc25 and Sox2

It appears that the expression patterns of Cdc25A and Sox2 were more similar at stage HH 10 in chick embryos. Sox2 mRNA expression was fairly plentiful in the caudal neural plate similaly to Cdc25A, which is different from the report of Uwanogho et al. (1995). Cdc25A mainly activates the CDK2/cyclin E and CDK2/cyclin A complexes during the G1-S transition (Jinno et al., 1994), but also has a role in the G2-M transition by activating CDK1/cyclin B complexes, which are thought to initiate chromosome condensation (Molinari et al., 2000; Boutros et al., 2007). The Cdc25A role is one of controlling cell proliferation regulator by regulating cell cycle progress.

Expression patterns of Cdc25 and Sox2 were overlapping in the CNS in HH stage 10. Sox2 can retain cell proliferation and/or initiate differentiation. Cdc25 participates in cell proliferation by regulating the checkpoint in cell cycle progress. Moreover, expression of both Cdc25A and Sox2 is regulated by STAT3 (signal transducer and activator of transcription).

Through the up-regulation of cell cycle and survival genes, STAT3 plays important roles in cell growth, antiapoptosis, and cell transformation. STAT3 and its transcriptional cofactors are recruited to the promoter of the Cdc25A gene to activate its expression. Myc and STAT3 cooperate to induce the expression of Cdc25A. However, STAT3 also functions as a transcriptional repressor of the Cdc25A gene. STAT3 forms a repressor complex with the retinoblastoma (Rb) tumor suppressor to occupy the Cdc25A promoter and block its induction (Barre et al., 2005). A novel signaling pathway exists during early neural development in which STAT3 directly regulates the Sox2 promoter leading to Sox2 expression. STAT3 and Sox2 are expressed in the same areas of developing neural tissue which suggests that STAT3 is capable of regulating nestin via Sox2 in vivo (Foshay and Gallicano, 2008).