Apr 28, 2017

TGF(beta) Mediated Structural Remodeling Facilitates Optic Fissure Fusion And The Necessity Of BMP Antagonism In This Process

bioRxiv
Max D KnickmeyerStephan Heermann

Abstract

The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Multiple factors are genetically linked to coloboma formation. However, especially the process of optic fissure fusion is still largely elusive on a cellular and molecular basis. We found a coloboma phenotype in mice with a targeted inactivation of the transforming growth factor(beta) 2 (TGF(beta)2). Here the optic fissure margins got in touch, however, failed to fuse. Transcriptomic analyses indicated TGF(beta) mediated ECM remodeling during optic fissure fusion. For functional analyses, we switched model systems and made use of zebrafish. We found TGF(beta) ligands expressed in the developing zebrafish eye, and the ligand binding receptor in the optic fissure. Using a new in vivo TGF(beta) signaling reporter, we also found active TGF(beta) signaling in the margins of the optic fissure. We addressed the function of Cadherin 6 (cdh6), one of the TGF(beta) regulated genes, by knock down experiments in zebrafish and found a prominent coloboma phenotype. Cdh6 was often found involved in processes of epithelial to mesenchymal transition...Continue Reading

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Mentioned in this Paper

Vertebrates
Recombinant Transforming Growth Factor
In Vivo
Regulation of Transforming Growth Factor Beta Activation
Fst
Transforming Growth Factor beta
Gene Knockdown Techniques
Reparative Closure
Ligand Binding
Extracellular Matrix Constituent Secretion

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