Gibby, K. A., McDonnell, K., Schmidt, M. O., Wellstein, A. (May 2009) A distinct role for secreted fibroblast growth factor-binding proteins in development. Proc Natl Acad Sci U S A, 106 (21). pp. 8585-8590.
Preview |
PDF (Paper)
McDonnell PNAS 2009.pdf - Published Version Download (793kB) | Preview |
Abstract
FGFs modulate diverse biological processes including embryonic development. Secreted FGF-binding proteins (BPs) can release FGFs from their local extracellular matrix storage, chaperone them to their cognate receptors, and thus modulate FGF signaling. Here we describe 2 chicken BP homologs (chBP) that show distinct expression peaks at embryonic days E7.5 () and E11.5 (), although their tissue distribution is similar (skin = intestine>lung>heart, liver). Embryos were grown ex ovo to monitor the phenotypic impact of a timed in vivo knockdown of expression peaks by microinjection of specific siRNAs targeted to either of the chBPs. Knockdown of peak expression of caused embryonic lethality within <5 days. Surviving embryos showed defective ventral wall closure indicative of altered dorsoventral patterning. This defect coincided with reduced expression of but not that are involved in the control of thoracic/abdominal segment morphology. Also, MAPK phosphatase 3, a negative regulator of FGF signaling, and that can participate in feedback control of the FGF pathway were reduced, reflecting altered FGF signaling. Knockdown of the expression peak caused embryonic lethality within <3 days although no distinct morphologic phenotype or pathways alterations were apparent. We conclude that BPs play a significant role in fine-tuning the complex FGF signaling network during distinct phases of embryonic development.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | body wall defect chick embryo siRNA Hox B Shh |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organism description > animal > developmental stage |
| CSHL Authors: | |
| Communities: | CSHL labs > Mittal lab |
| Depositing User: | Matt Covey |
| Date: | 26 May 2009 |
| Date Deposited: | 21 Feb 2013 17:45 |
| Last Modified: | 08 Nov 2017 20:48 |
| PMCID: | PMC2689014 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27363 |
Actions (login required)
 |
Administrator's edit/view item |