RESUMO
The endoderm and much of the mesoderm arise from the EMS cell in the four-cell C. elegans embryo. We report that the MED-1 and -2 GATA factors specify the entire fate of EMS, which otherwise produces two C-like mesectodermal progenitors. The meds are direct targets of the maternal SKN-1 transcription factor; however, their forced expression can direct SKN-1-independent reprogramming of non-EMS cells into mesendodermal progenitors. We find that SGG-1/GSK-3beta kinase acts both as a Wnt-dependent activator of endoderm in EMS and an apparently Wnt-independent repressor of the meds in the C lineage, indicating a dual role for this kinase in mesendoderm development. Our results suggest that a broad tissue territory, mesendoderm, in vertebrates has been confined to a single cell in nematodes through a common gene regulatory network.
Assuntos
Blastômeros/metabolismo , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endoderma/metabolismo , Proteínas de Helminto/metabolismo , Mesoderma/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra , Sequência de Aminoácidos , Animais , Sequência de Bases , Blastômeros/citologia , Caenorhabditis elegans/citologia , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Linhagem da Célula , Clonagem Molecular , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Endoderma/citologia , Fatores de Ligação de DNA Eritroide Específicos , Fatores de Transcrição GATA , Quinase 3 da Glicogênio Sintase , Proteínas de Helminto/química , Proteínas de Helminto/genética , Mesoderma/citologia , Dados de Sequência Molecular , Mutação/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/fisiologia , Proteínas de Ligação a RNA , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Proteínas WntRESUMO
C. elegans animals mutant for the unc-119 gene exhibit movement, sensory and behavioral abnormalities. Consistent with a nervous system role, unc-119 reporter genes are expressed throughout the C. elegans nervous system. The UNC-119 protein has strong sequence similarity to the predicted protein from a human gene, HRG4/HsUNC-119, whose transcript is abundant in the retina. Using these similarities, we have identified a Drosphila homolog, DmUNC-119, which is expressed in the Drosophila nervous system. The predicted C. elegans, human and Drosophila gene products are conserved across two domains. Expression of portions of HRG4/HsUNC-119 or DmUNC-119, directed by the unc-119 promoter, can fully rescue the C. elegans unc-119 mutant phenotype. We tested the ability of portions of HRG4/HsUNC-119 to rescue, and found that its function in C. elegans requires the conserved carboxyl terminus, while the dissimilar amino terminus is dispensable. UNC-119, HRG4 and DmUNC-119 constitute members of a new class of neural genes whose common function has been maintained through metazoan evolution.
