To investigate genes involved in cell division control in the embryonic endoderm lineage, we performed an RNAi based screen and identified several genes that, when inhibited, alter the wild type number of embryonic gut cells. Among the identified genes we chose five embryonic lethal genes for further analysis based on the penetrant elevation of gut cell numbers. Three of these five genes encode the C. elegans SNF-5, RPN-9, and CDC-37 orthologs. The other two (F40F11.2, C01A2.5) are not clear homologues of any known gene in other organisms. Quantification of one non-endodermal cell type (the seam cells) suggested that the hyperproliferation effect is not restricted to the gut for at least two genes (
cdc-37 and F40F11.2). Ablation of the E blastomere revealed that for four of the genes, the extra gut cells do not arise ectopically, while for the
cdc-37 ortholog, extra gut cells derive from normally non-endodermal lineages. Inhibition of the
cdc-37 gene also causes abnormalities in the timing and pattern of early cell divisions, resulting in mis-positioning and morphological defects of the blastomeres. We analyzed the F40F11.2 in further depth and found that the total number of embryonic nuclei is elevated in some mutant embryos, suggesting a general effect of hyperproliferation in other tissues besides the gut, albeit at low penetrance. A BLASTP search revealed the presence of a domain with significant homology to a region of the GLTSCR1 (human Glioma Tumor Suppressor Candidate Region Gene 1) protein, which is relatively conserved among different phyla. Lineage analysis in embryos in which F40F11.2 gene was inhibited by RNAi confirmed that the extra gut cells arise within the endoderm lineage. The Worm Interactome database suggests that the predicted protein encoded by F40F11.2 interacts with other proteins, suggesting a network of protein interactions that may explain the observed RNAi phenotypes of this gene.