PUBLICATION

Gut feelings: Molecular and genetic analysis of endoderm development in zebrafish

Authors
Alexander, J.P.
ID
ZDB-PUB-021016-63
Date
1999
Source
Ph.D. Thesis : (Thesis)
Registered Authors
Alexander, Jon
Keywords
none
MeSH Terms
none
PubMed
none
Abstract
The mechanisms that underlie the formation of the endoderm in vertebrates have only recently begun to be explored. Using the molecular and genetic methods available in zebrafish I have investigated several aspects of this problem. I first demonstrate an essential role for the zebrafish locus casanova in the initial formation of the endoderm. casanova mutants lack a gut tube, show no molecular evidence of regional endodermal differentiation, and appear to lack endoderm entirely from the onset of gastrulation. Mosaic analysis indicates that casanova functions cell-autonomously within the endodermal progenitors. I have then used overexpression studies in wild-type and different mutant zebrafish embryos to assemble a genetic pathway that underlies formation of the zebrafish endoderm. My data suggest that nodal-related TGF-? growth factors together with the One-eyed pinhead protein act through type I TGF-? receptors such as TARAM-A to induce and maintain the expression of the gene mixer . Mixer, in a manner that depends upon casanova, then promotes expression of the sox17 gene, initiating the process of endoderm differentiation. I also describe molecular and genetic evidence that indicate an important distinction between the gut endoderm and the pharyngeal endoderm in zebrafish, and suggest that the pharyngeal endoderm may in fact be mesodermal in origin. Lastly, I have begun to investigate the role of bone morphogenetic proteins in endoderm development. My results suggest that bone morphogenetic proteins may play a role in both the formation and anterior-posterior patterning of the endoderm in zebrafish, providing the first evidence of an endogenous role for these factors in vertebrate endoderm development.
Errata / Notes
Ph.D. Thesis, University of California, San Francisco
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping