Regulation of Avian Gastrulation by Fibroblast Growth Factor, Non-Canonical Wnt, and Eph-Ephrin Signaling Pathways

Persistent Link:
http://hdl.handle.net/10150/195983
Title:
Regulation of Avian Gastrulation by Fibroblast Growth Factor, Non-Canonical Wnt, and Eph-Ephrin Signaling Pathways
Author:
Hardy, Katharine
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Gastrulation is a key early developmental event that generates the three primary germ layers (ectoderm, mesoderm, and endoderm) from which organ systems subsequently develop. The physical mechanisms of germ layer formation differ significantly in amniotes (reptiles, birds, and mammals) and anamniotes (e.g. frog and fish), as amniote gastrulation includes an epithelial-mesenchymal transition (EMT) that is absent from anamniote gastrulation. Despite this striking difference, much of our knowledge regarding the mechanisms underlying gastrulation is derived from frog and fish studies. To better understand amniote gastrulation, the work herein investigates three signaling pathways that regulate amniote gastrulation with distinct and overlapping functions. The central hypothesis is that multiple signaling pathways function cooperatively to precisely modulate cell migration through the primitive streak during avian gastrulation.First, I describe a novel function of Fibroblast Growth Factor (FGF) signaling in the preingression epiblast adjacent to the avian primitive streak, where it governs the expression of molecules from diverse signaling pathways and transcription factor families, and which is mediated largely through the Ras/MAPK pathway. Importantly, FGF signaling also regulates cell migration during avian gastrulation.Next, I report the isolation of a novel chicken non-canonical Wnt ligand (Wnt11b) that is specifically expressed in the primitive streak and adjacent preingression epiblast during gastrula stages. In gain and loss of function studies, Wnt11b and Wnt5a/b participate in regulating cell migration through the streak in a largely redundant fashion. Signaling specifically targets the non-canonical pathway, as similar cell migration defects are observed with a non-canonical mutant of Dishevelled, and activating the canonical pathway has no effect on cell migration.Finally, I investigate the function of A-class Eph-ephrin signaling during avian gastrulation, and describe that Eph receptor forward signaling negatively regulates the migration of cells through the primitive streak. This modulation of cell migration occurs independently of the EMT that accompanies avian gastrulation, as cells are able to undergo the normal cadherin transition and the basal lamina is unaffected.Altogether, the work presented herein provides a significant contribution to our understanding of signaling pathways that modulate gene expression and ongoing cell migration during germ layer formation in amniote gastrulation.
Type:
text; Electronic Dissertation
Keywords:
gastrulation; chicken; cell signaling; EMT
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Cell Biology & Anatomy; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Antin, Parker B.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleRegulation of Avian Gastrulation by Fibroblast Growth Factor, Non-Canonical Wnt, and Eph-Ephrin Signaling Pathwaysen_US
dc.creatorHardy, Katharineen_US
dc.contributor.authorHardy, Katharineen_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractGastrulation is a key early developmental event that generates the three primary germ layers (ectoderm, mesoderm, and endoderm) from which organ systems subsequently develop. The physical mechanisms of germ layer formation differ significantly in amniotes (reptiles, birds, and mammals) and anamniotes (e.g. frog and fish), as amniote gastrulation includes an epithelial-mesenchymal transition (EMT) that is absent from anamniote gastrulation. Despite this striking difference, much of our knowledge regarding the mechanisms underlying gastrulation is derived from frog and fish studies. To better understand amniote gastrulation, the work herein investigates three signaling pathways that regulate amniote gastrulation with distinct and overlapping functions. The central hypothesis is that multiple signaling pathways function cooperatively to precisely modulate cell migration through the primitive streak during avian gastrulation.First, I describe a novel function of Fibroblast Growth Factor (FGF) signaling in the preingression epiblast adjacent to the avian primitive streak, where it governs the expression of molecules from diverse signaling pathways and transcription factor families, and which is mediated largely through the Ras/MAPK pathway. Importantly, FGF signaling also regulates cell migration during avian gastrulation.Next, I report the isolation of a novel chicken non-canonical Wnt ligand (Wnt11b) that is specifically expressed in the primitive streak and adjacent preingression epiblast during gastrula stages. In gain and loss of function studies, Wnt11b and Wnt5a/b participate in regulating cell migration through the streak in a largely redundant fashion. Signaling specifically targets the non-canonical pathway, as similar cell migration defects are observed with a non-canonical mutant of Dishevelled, and activating the canonical pathway has no effect on cell migration.Finally, I investigate the function of A-class Eph-ephrin signaling during avian gastrulation, and describe that Eph receptor forward signaling negatively regulates the migration of cells through the primitive streak. This modulation of cell migration occurs independently of the EMT that accompanies avian gastrulation, as cells are able to undergo the normal cadherin transition and the basal lamina is unaffected.Altogether, the work presented herein provides a significant contribution to our understanding of signaling pathways that modulate gene expression and ongoing cell migration during germ layer formation in amniote gastrulation.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectgastrulationen_US
dc.subjectchickenen_US
dc.subjectcell signalingen_US
dc.subjectEMTen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineCell Biology & Anatomyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairAntin, Parker B.en_US
dc.contributor.committeememberGregorio, Carolen_US
dc.contributor.committeememberHeimark, Ronalden_US
dc.contributor.committeememberKrieg, Paulen_US
dc.contributor.committeememberRunyan, Raymonden_US
dc.contributor.committeememberStamer, W. Danielen_US
dc.identifier.proquest2913en_US
dc.identifier.oclc659749562en_US
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