Asymmetric cell division is a primary mechanism for generating neuronal diversity in C. elegans. A novel protein, HAM-1, is asymmetrically distributed in many mitotic embryonic cells and participates in the divisions of several neuroblasts. For example, the HSN/PHB neuroblast (ABpl/rapppap) divides asymmetrically. In wild type, its anterior daughter dies and its posterior daughter becomes the HSN/PHB precursor. However, in loss-of-function
ham-1 mutants, both daughters can adopt an HSN/PHB precursor-like fate resulting in extra HSN and PHB neurons. This phenotype is incompletely penetrant; often the daughter cell fated to die will still die in
ham-1 mutants, but aspects of its death may be abnormal such as delayed onset or inappropriate corpse persistence. With the overall goal of identifying additional components involved in the proper execution of the HSN/PHB lineage, we conducted genetic screens for mutants with extra PHBs. New alleles of
ham-1 were isolated in these screens, and subsequent analysis of all available alleles has helped elucidate the role HAM-1 plays in asymmetric cell division. We find that HAM-1 can interact with itself in the yeast two-hybrid system, but the missense mutation
ham-1(
n1811) disrupts this interaction and the ability of the HAM-1 protein to localize at the cell periphery. Together, these data suggest that HAM-1 multimerization may be necessary for its proper localization. Furthermore, lineage analysis using the nonsense mutant,
ham-1(
gm279), has allowed us to identify additional defects in the HSN/PHB neuroblast division. The daughter cells of this division often end up oriented abnormally along the A/P axis in
ham-1(
gm279) embryos. When the anterior daughter does die, its corpse is aberrantly large. Together, these data suggest that HAM-1 may control the positioning of the HSN/PHB neuroblast spindle. We also note that many of the other corpses in
ham-1(
gm279) embryos are unusually large, suggesting that
ham-1 plays a major role in asymmetric cell division at this stage of development. Our screens have also identified new alleles of
ced-3 (caspase),
egl-5 (homeodomain),
egl-27 (MTA1/NURD complex),
lin-32 (bHLH protein), and
hlh-14 (bHLH protein). All of these genes play roles in the proper execution of the HSN/PHB lineage. We have performed a number of follow-up experiments to pinpoint the functions of these genes in neuroblast divisions.