Lamb Helen, Fernholz McKenzi, Liro Małgorzata J, Myles Krista M, Anderson Holly, Rose Lesilee S
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Biochemistry, Molecular, Cell and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616, USA.
Genetics. 2025 Apr 17;229(4). doi: 10.1093/genetics/iyaf020.
Asymmetric cell division is essential for the creation of cell types with different identities and functions. The endomesodermal precursor cell (EMS) of the 4-cell Caenorhabditis elegans embryo undergoes an asymmetric division in response to partially redundant signaling pathways. One pathway involves a Wnt signal from the neighboring P2 cell, while the other pathway is defined by the receptor-like MES-1 transmembrane protein localized at the EMS-P2 cell contact and the cytoplasmic kinase SRC-1. In response to these signals, the EMS nuclear-centrosome complex rotates, so that the spindle forms on the anterior-posterior axis; after division, the daughter cell contacting P2 becomes the endodermal precursor cell. Here, we identify the Rac1 homolog CED-10 as a new component of the MES-1/SRC-1 pathway. Loss of CED-10 affects both spindle positioning and endoderm specification in the EMS cell. SRC-1 dependent phosphorylation at the EMS-P2 contact is reduced. However, the asymmetric division of the P2 cell, which is also MES-1 and SRC-1 dependent, appears normal in ced-10 mutants. These and other results suggest that CED-10 acts upstream of, or at the level of, SRC-1 activity in the EMS cell. In addition, we find that the branched actin regulator ARX-2 is enriched at the EMS-P2 cell contact site, in a CED-10-dependent manner. Loss of ARX-2 results in EMS spindle orientation defects, suggesting that CED-10 acts through branched actin to promote spindle orientation in the EMS cell.
不对称细胞分裂对于产生具有不同特性和功能的细胞类型至关重要。秀丽隐杆线虫4细胞胚胎的内中胚层前体细胞（EMS）会响应部分冗余的信号通路进行不对称分裂。一条通路涉及来自相邻P2细胞的Wnt信号，而另一条通路则由定位于EMS-P2细胞接触部位的受体样MES-1跨膜蛋白和细胞质激酶SRC-1所定义。响应这些信号时，EMS核中心体复合物会旋转，从而使纺锤体沿前后轴形成；分裂后，与P2接触的子细胞成为内胚层前体细胞。在此，我们鉴定出Rac1同源物CED-10是MES-1/SRC-1通路的一个新组分。CED-10的缺失会影响EMS细胞中的纺锤体定位和内胚层特化。EMS-P2接触部位的SRC-1依赖性磷酸化作用会降低。然而，同样依赖MES-1和SRC-1的P2细胞的不对称分裂在ced-10突变体中看起来是正常的。这些以及其他结果表明，CED-10在EMS细胞中作用于SRC-1活性的上游或处于该活性水平。此外，我们发现分支肌动蛋白调节因子ARX-2以CED-10依赖性方式富集于EMS-P2细胞接触位点。ARX-2的缺失会导致EMS纺锤体定向缺陷，这表明CED-10通过分支肌动蛋白来促进EMS细胞中的纺锤体定向。
