Znosko, Wade
(2010)
OVERLAPPING FUNCTIONS OF PEA3 ETS TRANSCRIPTION FACTORS IN FGF SIGNALING DURING ZEBRAFISH DEVELOPMENT.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Fibroblast Growth Factors (FGFs) are secreted molecules that activate the RAS/mitogen-activated protein kinase (MAPK) signaling pathway to establish dorsal polarity, maintain the isthmic organizer, and assure proper ventricle formation in the zebrafish. The mechanism of FGF regulation of these processes and the transcription factors involved are still unclear. Expression of the zebrafish PEA3 family of ETS transcription factors, Etv5, Erm, and Pea3, is responsive to FGF signaling, and these factors are likely transcriptional effectors of this pathway. I have determined the role of PEA3 ETS factors in FGF signaling and gene regulation through gain- and loss-of-function studies. Ectopic expression of a constitutively activated form of Etv5 induced FGF target transcripts, dual specificity phosphatase 6 (dusp6) and similar expression to fgfs (sef). The simultaneous knock-down of Etv5, Erm, and Pea3 produced phenotypes reminiscent of the fgf8 mutant, including the disruption of the mid-hindbrain boundary, diminished cardiac progenitors, and left/right patterning defects. Furthermore, the expression of FGF target genes was abolished in Etv5/Erm/Pea3 depleted embryos. To understand how FGF signaling and PEA3 ETS factors control gene expression, the transcriptional regulation of dusp6 was studied in mouse and zebrafish. Conserved Pea3/ETS binding sites were identified within the dusp6 promoter, and reporter assays show that one of these sites is required for dusp6 induction by FGFs in both species. In addition, I demonstrated the interaction of PEA3 ETS factors with the dusp6 promoter both in vitro and in vivo. These results revealed the requirement of ETS factors in transducing FGF signals in developmental processes.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
1 October 2010 |
| Date Type: |
Completion |
| Defense Date: |
1 June 2010 |
| Approval Date: |
1 October 2010 |
| Submission Date: |
30 June 2010 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
cilia; FGF signaling; Kupffer's vesicle; L/R asymmetry; PEA3 ETS factors; zebrafish |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-06302010-114141/, etd-06302010-114141 |
| Date Deposited: |
10 Nov 2011 19:49 |
| Last Modified: |
15 Nov 2016 13:45 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8241 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}