Seah Adeline, Sternberg Paul W
California Institute of Technology, Pasadena, 91125, USA.
BMC Dev Biol. 2009 Dec 31;9:74. doi: 10.1186/1471-213X-9-74.
During development, different signaling pathways interact to specify cell fate by regulating transcription factors necessary for fate specification and morphogenesis. In Caenorhabditis elegans, the EGF-Ras and Wnt signaling pathways have been shown to interact to specify cell fate in three equivalence groups: the vulval precursor cells (VPCs), the hook competence group (HCG) and P11/12. In the VPCs, HCG and P11/12 pair, EGF and Wnt signaling positively regulate different Hox genes, each of which also functions during fate specification. In the male, EGF-Ras signaling is required to specify the Bgamma fate within the Bgamma/delta equivalence pair, while Notch signaling is required for Bdelta fate specification. In addition, TGF-beta signaling by dbl-1/dpp controls ceh-13/labial/Hox1 expression in Bgamma.
We show that EGF-Ras signaling is required for Bgamma expression of ceh-13/labial/Hox1. The transcription factors lin-1/ETS and lin-31/Forkhead, functioning downstream of the EGF pathway, as well as sur-2/MED23 (a component of the Mediator complex) also control ceh-13 expression in Bgamma. In addition, our results indicate that lin-44/Wnt, mom-2/Wnt and lin-17/Fz are necessary to maintain the division of Bgamma along a longitudinal axis. We also show that dbl-1/dpp acts either in parallel or downstream of EGF pathway to regulate ceh-13/Hox1 expression in Bgamma. Lastly, we find that a dbl-1/dpp null mutation did not cause any vulval or P12 defects and did not enhance vulval and P12 defects of reduction-of-function mutations of components of the EGF pathway.
ceh-13/labial/Hox1 expression in Bgamma is regulated by the EGF pathway and downstream factors lin-1/ETS lin-31/Forkhead and sur-2/MED23. Wnt signaling is required for proper Bgamma division, perhaps to orient the Bgamma mitotic spindle. Our results suggest that dbl-1/dpp is not required for VPC and P12 specification, highlighting another difference among these EGF-dependent equivalence groups.
在发育过程中,不同的信号通路相互作用,通过调节细胞命运特化和形态发生所需的转录因子来确定细胞命运。在秀丽隐杆线虫中,已表明表皮生长因子受体(EGF)-Ras和Wnt信号通路相互作用,以在三个等价组中确定细胞命运:外阴前体细胞(VPCs)、钩状感受态组(HCG)和P11/12。在VPCs、HCG和P11/12对中,EGF和Wnt信号正向调节不同的Hox基因,每个基因在细胞命运特化过程中也发挥作用。在雄性中,需要EGF-Ras信号来确定Bγ/δ等价对中的Bγ命运,而Notch信号是确定Bδ命运所必需的。此外,dbl-1/dpp介导的转化生长因子-β(TGF-β)信号控制Bγ中ceh-13/唇状/Hox1的表达。
我们表明,EGF-Ras信号是ceh-13/唇状/Hox1在Bγ中表达所必需的。在EGF信号通路下游发挥作用的转录因子lin-1/ETS和lin-31/叉头,以及sur-2/MED23(中介体复合物的一个组分)也控制Bγ中ceh-13的表达。此外,我们的结果表明,lin-44/Wnt、mom-2/Wnt和lin-17/Fz对于维持Bγ沿纵轴的分裂是必需的。我们还表明,dbl-1/dpp在EGF信号通路的平行方向或下游发挥作用,以调节Bγ中ceh-13/Hox1的表达。最后,我们发现dbl-1/dpp基因敲除突变不会导致任何外阴或P12缺陷,也不会增强EGF信号通路组分功能缺失突变引起的外阴和P12缺陷。
Bγ中ceh-13/唇状/Hox1的表达受EGF信号通路及其下游因子lin-1/ETS、lin-31/叉头和sur-2/MED23的调节。Wnt信号对于Bγ的正常分裂是必需的,可能是为了使Bγ有丝分裂纺锤体定向。我们的结果表明,VPC和P12的特化不需要dbl-1/dpp,这突出了这些依赖EGF的等价组之间的另一个差异。