The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1 to activate C. elegans endoderm development

Dev Biol. 2005 Sep 15;285(2):510-23. doi: 10.1016/j.ydbio.2005.06.022.

Abstract

POP-1, a Tcf/Lef-1-like target of the convergent Wnt and MAP kinase (MAPK) signaling pathways, functions throughout Caenorhabditis elegans development to generate unequal daughters during asymmetric cell divisions. A particularly prominent such asymmetric division occurs when the EMS blastomere divides to produce MS, a mesoderm precursor, and E, the sole endoderm progenitor. POP-1 allows mesoderm development in the MS lineage by repressing the endoderm-promoting end-1 and end-3 genes. This repression is relieved in the E lineage by Wnt/MAPK signaling, which results in phosphorylation and export of POP-1 from the E nucleus. Here, we report that, in addition to repressing E development in MS, POP-1 also functions positively in endoderm development, in conjunction with the well-characterized endoderm-promoting SKN-1-->MED regulatory cascade. While removal of POP-1 alone results in derepression of endoderm development in the MS lineage, mutations in several genes that result in impenetrant loss of endoderm are strongly enhanced by loss of pop-1 function. A Lef-1-like binding site is essential for activation of an end-1 promoter fusion, suggesting that POP-1 may act directly on end-1. Thus, POP-1 may generate developmental asymmetry during many cell divisions in C. elegans by reiteratively switching from repressive and activating states. Furthermore, we report that the Caudal-like homeodomain protein PAL-1, whose role in early embryogenesis was thought to be exclusive specification of mesectodermal development in the lineage of the C blastomere, can act with POP-1 to activate endoderm specification in the absence of the SKN-1-->MED transcriptional input, accounting for the impenetrance of mutants lacking SKN-1 or MED-1,2 activity. We conclude that the combined action of several separate transcriptional regulatory inputs, including SKN-1, the MEDs, PAL-1, and the Wnt/MAPK-activated form of POP-1, are responsible for activating end gene transcription and endoderm development.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Division / physiology*
  • DNA-Binding Proteins / metabolism*
  • Embryonic Induction / physiology*
  • Endoderm / physiology*
  • GATA Transcription Factors / metabolism
  • Galactosides
  • High Mobility Group Proteins / metabolism*
  • Homeodomain Proteins / metabolism*
  • Indoles
  • RNA Interference
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • END-1 protein, C elegans
  • GATA Transcription Factors
  • Galactosides
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Indoles
  • Trans-Activators
  • Transcription Factors
  • pop-1 protein, C elegans
  • pal-1 protein, C elegans
  • skn-1 protein, C elegans
  • 5-bromo-4-chloro-3-indolyl beta-galactoside