Year: 2006
Type: dissertation
Abstract: In vertebrate embryonic development, correct specification of tissue fates along the\ndorsoventral (D/V) axis is known to require the secreted signaling ligand Wnt8. Wnt8\nsignaling promotes ventral fates and antagonizes the expansion of the dorsal domain\nknown as the organizer. Maintenance of the organizer is critical for proper development\nas this tissue is known to produce inhibitors of Wnt and BMP (Bone Morphogenetic\nProtein) family ligands; BMPs are also known to play a major role in promoting ventral\nfates. In order to understand how Wnt8 antagonizes the organizer, we analyzed the\nepistatic relationship between Wnt8 and the transcriptional repressors Vent and Vox\nusing zebrafish as a model organism. We found that Wnt8/β-catenin signaling directly\nregulates the transcriptional levels of vent and vox so that they can repress the\ntranscription of dorsal genes on the ventral side of the embryo. To understand the\ncontribution of Wnt8 towards ventral fate specification, we carefully analyzed its\nrelationship with BMP signaling during gastrula stages. We found that bmp expression\nin the mesoderm is under the control of Wnt8 at mid-gastrulation and that regulation of\nbmp explains many of the ventral defects observed in wnt8 mutants. Antagonism of the\nexpression of organizer-derived BMP inhibitors by Wnt8 also indirectly allows timely\nBMP signaling. Analysis of wnt8; bmp double mutants revealed an early unsuspected\nfunction of BMP in the antagonism of the organizer. Further, we uncovered a\nmechanism through which regulation of vent, vox and a related-gene ved expression by\nboth Wnt8 and BMP antagonizes dorsal/axial mesoderm identity to preserve the integrity\nof ventral/non-axial tissues. In summary, we have revealed some of the mechanisms of\nWnt8 function in D/V mesoderm patterning: it restricts the organizer domain by\nregulating vent and vox, it allows BMP induced differentiation through its inhibition of\nBMP antagonists derived from the organizer and it co-regulates vent, vox, and ved with\nBMP signaling to allow maintenance of the non-axial domain.
Author: Marie‐Christine Ramel
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2298408870