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

• DOI: 10.1016/j.ydbio.2005.06.022
• Publication Date: 2005-08-10T14:08:39Z
• Authors: Morris F. Maduro; Jodie J. Kasmir; Jiangwen Zhu; Joel H. Rothman
• Keywords: 0301 basic medicine; PAL-1; Indoles; Wnt pathway; GATA Transcription Factors; 03 medical and health sciences; POP-1; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Molecular Biology; Embryonic Induction; Homeodomain Proteins; 0303 health sciences; Endoderm; High Mobility Group Proteins; Galactosides; Cell Biology; DNA-Binding Proteins; TCF/LEF factors; Trans-Activators; Asymmetric cell division; Germ layers; RNA Interference; Cell Division; Developmental Biology; Signal Transduction; Transcription Factors

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.