A conserved C. elegans zinc finger homeodomain protein, ZFH-2, is continuously required for the structural integrity and function of the alimentary tract and gonad.

An unusually large transcription factor arose at the base of bilaterian evolution through domain shuffling that recombined many copies of two distinct DNA-binding domains, C2H2-type zinc fingers and homeodomains. The function of this deeply conserved type of protein remains poorly characterized. We describe here the complete and complex expression pattern of its sole Caenorhabditis elegans representative, ZFH-2, throughout development and adulthood. We show that animals lacking this protein display defects in proper alimentary tract formation and starve to death in the first larval stage with an apparent inability to ingest food. Conditional removal of ZFH-2 at post-developmental stages reveals a continuous function of this protein in enabling food ingestion and demonstrates additional essential functions for the formation of other, post-embryonically generated tubular structures. Even though ZFH-2 is broadly expressed throughout the nervous system, we detected no obvious defects in neuronal development or function in zfh-2 null mutants. Genome-engineered alleles indicate that, although a large part of the protein is dispensable, at least a subset of the homeodomains are critical determinants for the essential functions of this protein.