The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1 to activate C. elegans endoderm development.
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.
Maduro
Morris F
MF
Department of MCD Biology and Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
Kasmir
Jodie J
JJ
Zhu
Jiangwen
J
Rothman
Joel H
JH
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004627:Embryonic Induction / Q000502:physiology*; D004707:Endoderm / Q000502:physiology*; D050980:GATA Transcription Factors / Q000378:metabolism; D005697:Galactosides; D006609:High Mobility Group Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007211:Indoles; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C109211:END-1 protein, C elegans; D050980:GATA Transcription Factors; D005697:Galactosides; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D007211:Indoles; D015534:Trans-Activators; D014157:Transcription Factors; C096787:pop-1 protein, C elegans; C068665:pal-1 protein, C elegans; C073702:skn-1 protein, C elegans; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside