The Caenorhabditis elegans male tail tip is a simple yet powerful model in which to study morphogenesis. The tail tip is constructed by hypodermal cells 8-11. In both males and hermaphrodites the tail tip takes on the appearance of a tapered cone at the beginning of L4. Later in L4, within males, the cells fuse and retract away from the overlying cuticle. By adulthood, these cells have retracted fully, forming the normal, rounded, peloderan (Pel) phenotype. Alleles of several genes have been isolated where males retain the pointed tail tip of the L4 into adulthood and retraction, fusion or both never take place, thus resulting in the leptoderan (Lep) phenotype. Mutant genes that result in this phenotype have been shown to play key roles in some well characterized developmental pathways, specifically the heterochronic, sex determination, and Wnt signaling pathways1-3. Here, we report a newly discovered role for the posterior hox genes in male tail tip morphogenesis. We have been conducting a whole-genome RNAi screen via feeding to identify all the genes or genetic pathways involved in this process. We have screened all of chromosomes III and IV and identified 35 positives that fall into 2 distinct categories: Lep or over-retracted (Ore). The latter phenotype could result from a retraction that happened either too early, too quickly or for too long a time period. Two genes that were identified in this primary screen are the posterior Hox genes
php-3 and
nob-1. Treating L1 C. elegans males with RNAi directed against either or both of these genes results in a striking disruption in retraction and fusion during the development of the tail tip. We have evidence for a cooperative post-embryonic role for
php-3 and
nob-1 in tail tip development. In
php-3 mutants, it appears that
hyp9 and
hyp10 fuse while
hyp11 and
hyp8 fail to fuse. However, transcription of the fusogen gene
eff-14 is unaffected, possibly suggesting that other genes downstream of
php-3 may also be required for fusion. In addition, we have shown that a key downstream regulator of the sex determination pathway,
dmd-33, is positively regulated by both posterior hox genes. Future work will be directed towards determing exactly how the posterior Hox genes interact with the other pathways that are known to regulate male tail tip morphogenesis.