Dissertation/Thesis Abstract

Patterning the vertebrate mesoderm: Functional analysis of bone morphogenetic protein-responsive genes in vasculogenesis and kidney development
by Kamei, Caramai Nanae, Ph.D., Harvard University, 2010, 97; 3395431
Abstract (Summary)

To identify relevant BMP targets, and thereby to elucidate pathways leading to specific cell fates downstream of BMP signaling, we analyzed explants of chick somitic precursors treated with BMP. We found that the zinc finger transcription factor GATA5 is highly expressed following exposure to BMP. The first blood vessels in the embryo are normally produced by angioblasts specified on the ventral side of the lateral plate mesoderm in a process called vasculogenesis. Using in vivo electroporation techniques, we found that ectopic expression of GATA5 or the related family members GATA4 and GATA2 in somitic precursors drives cells to participate in vasculogenesis at the expense of a somitic cell fate. The GATA4 DNA binding domain fused to the constitutive transcriptional activator VP-16 mimics over-expression of GATA factors, indicating that GATA factors act as transcriptional activators in this context. These data suggest a role for GATA factors as downstream mediators of BMP signaling and in particular in the BMP pathway driving cells toward a vascular endothelial fate.

Another transcriptional mediator of BMP signaling in the mesoderm is the zinc finger-containing transcription factor Odd-skipped related 1 (Odd1/Osr1). Odd1 is highly expressed in response to intermediate levels of BMP and is the earliest known marker of the intermediate mesoderm, the precursor to all kidney tissue. Formation of kidney tissue requires the specification of mesenchymal kidney precursor cells and their subsequent differentiation into epithelial structures such as the nephric duct or nephric tubules. Odd1 is localized to mesenchymal precursors within the mesonephric and metanephric kidney and is subsequently down-regulated upon nephric duct and tubule differentiation. Mice lacking Odd1 do not form metanephric mesenchyme, and do not express several other factors required for metanephric kidney formation including Eya1, Six2, Pax2, Sall1, and Gdnf. In transient ectopic expression experiments in the chick embryo, Odd1 can promote expression of the metonephric precursor markers Pax2 and Lim1. Finally, persistent expression of Odd1 in nephric precursor cells inhibits differentiation of these precursors into kidney tubules. These data indicate that Odd1 plays an important role in the specification of kidney precursor cells and in regulating their differentiation into kidney tubular tissue.

Indexing (document details)
Advisor: Tabin, Clifford J.
Commitee:
School: Harvard University
School Location: United States -- Massachusetts
Source: DAI-B 71/02, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Genetics, Evolution and Development
Keywords: Bone morphogenetic proteins, Kidney development, Mesoderm, Vasculogenesis
Publication Number: 3395431
ISBN: 9781109636185
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