Asymmetric cell division is an important mechanism to generate cellular diversity. In order to investigate molecular mechanisms of asymmetric cell division, we have been focusing on the T hypodermal cell. The T cell undergoes asymmetric cell division, in which the anterior daughter generates hypodermal cells whereas the posterior daughter generates neural cells. It has been shown that the polarity of the T cell required for the asymmetric cell division is controlled by LIN-44/Wnt that is expressed on the posterior side of the T cell. Now we report that three genes;
psa-3/Meis,
ceh-20/Pbx and
nob-1/Hox are involved in asymmetric cell division of the T cell. In mutants of these genes, the posterior daughters of the T cell generate hypodermal cells instead of neural cells. Interestingly, expression of PSA-3/Meis was the stronger in the posterior daughter of the T cell than in the anterior daughter. A genomic fragment of the
psa-3/Meis gene upstream the first exon (~400bps) is sufficient for the asymmetry of
psa-3/Meis expression. In addition, a consensus binding site for the transcriptional factor POP-1/TCF within the promoter region is necessary for expression of
psa-3/Meis. Furthermore, the asymmetry of PSA-3/Meis expression was perturbed in
lin-44/Wnt or
lin-17/Frizzeled mutants. Because
pop-1/TCF was previously reported to be reqired for asymmetric cell division of the T cell, we conclude that
psa-3/Meis is a direct target of Wnt signaling and functions as a cell fate determinant in asymmetric cell division. In
nob-1/Hox or
ceh-20/Pbx mutants, we also found that expression of
psa-3/Meis in the T cell lineage was remarkably reduced. This data suggests that, in addition to Wnt signaling, NOB-1/Hox and CEH-20/Pbx regulate expression of
psa-3/Meis. Taken together, these data indicate that expression of
psa-3/Meis is controlled by binary mechanisms; Wnt signaling that establishes cellular polarity, and regulation of positional identity by Hox-Pbx complex. In addition to regulation of
psa-3/Meis expression, CEH-20/Pbx and NOB-1/Hox proteins may also form a ternary complex with PSA-3/Meis, because in other metazoans Meis and Pbx directly bind Hox as co-factors. Besides, we found that PSA-3/Meis directly interacted with CEH-20/Pbx and NOB-1/Hox in vitro. PSA-3/Meis may function as a cell fate determinant by complex formation with CEH-20/Pbx and NOB-1/Hox in asymmetric cell division of the T cell.