Spatial regulation of pho-1 expression in the Caenorhabditis elegans intestine

The pho-1 gene encodes a major intestinal acid phosphatase that is GPI-anchored at the edge of the intestinal lumen in the nematode Caenorhabditis elegans (C. elegans ). Loss of pho-1 activity is lethal. Its expression is regulated in a delicate temporal and spatial pattern during intestine development.;This thesis shows the necessity of a cis-acting sequence, ACTGATAA, and a GATA transcription factor, ELT-2, for pho-1 expression. ELT-2, the predominant regulator driving endoderm differentiation, initiates intestinal gene expression during the early phase of endoderm specification together with two redundant genes end-1 and end-3. During later phases, elt-2 is solely responsible for intestinal gene expression.;A summary of the current understanding of the transcriptional regulation of pho-1, providing insight into a potentially basic mechanism of maintaining anterior-posterior (A/P) polarity in the C. elegans intestine, will also be presented. The heterochronic gene lin-14 encodes a nuclear protein governing stage-specific temporal development by directly binding to its target DNA promoter. Here, I report that lin-14 affects spatial rather than temporal pho-1 regulation; depleting lin-14 activity by RNA-mediated interference (RNAi) or by mutation of a LIN-14 consensus binding site in the pho-1 promoter abolishes the A/P patterning of pho-1 and possibly other intestinal-specific genes after hatching. I also identify cdk-4 as another gene required for spatial patterning of pho-1. The exact mechanism of lin-14 and cdk-4 regulation of pho-1 patterning is currently unclear but these observations allow us to postulate that these two genes coordinate with a zygotic Writ pathway, components of which were previously shown to regulate the A/P polarity of intestine and the expression of at least two intestinal genes.