Abstract
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.