High impact information on pha-4

• Here we show that the pha-4 locus establishes organ identity for the Caenorhabditis elegans pharynx [1].
• In pha-4 mutants, pharyngeal cells are transformed into ectoderm [1].
• Conversely, ectopic pha-4 expression produces excess pharyngeal cells. pha-4 encodes an HNF-3 homolog selectively expressed in the nascent digestive tract, including all pharynx precursors at the time they are restricted to a pharyngeal fate [1].
• We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development [2].
• Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut [2].

Biological context of pha-4

• pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in organogenesis of the C. elegans pharynx [2].
• The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3alpha,beta,gamma genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis [2].
• We describe the molecular characterization of five pha-4 mutations and characterize their associated phenotypes [3].
• A missense mutation predicted to alter the PHA-4 amino terminus leads to a dramatic reduction in pha-4 activity even though the protein is expressed appropriately [3].
• Most other tissues are generated normally in pha-4 mutants, including cells related to pharyngeal cells by cell lineage and position [4].

Anatomical context of pha-4

• Multimerized de209 enhances transcription similarly to DE3 specifically in the pharyngeal muscles, suggesting it may be an essential site regulating ceh-22. de209 binds the pan-pharyngeal Forkhead factor PHA-4 in vitro and responds to ectopic pha-4 expression in vivo, suggesting that PHA-4 directly initiates ceh-22 expression through de209 [5].

Other interactions of pha-4

• Our analysis suggests that a positive feedback loop between tbx-2 and pha-4 is required for ABa-derived precursors to commit to pharyngeal muscle fate [6].
• We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells, while the forkhead transcription factor pha-4 is a target in the intestine [7].
• Moreover, the pharynx/tail expression of the WGATAR-deleted ges-1 transgene is abolished by mutations in the zygotic gene pha-4 [8].
• Inactivation of let-363/TOR or ruvb-1 suppresses the lethality associated with reduced pha-4 activity [9].

References