The Rac1 homolog CED-10 is a component of the MES-1/SRC-1 pathway for asymmetric division of the Caenorhabditis elegans EMS blastomere.

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.