Interplay of TGFb superfamily members governs optic fissure closure

Stephan Heermann; Priska Eckert; Juan L Mateo; Eleni Roussa; Belal Rahhal; Aimee Zuniga; Kerstin Krieglstein; Joachim Wittbrodt

doi:10.1101/010652

bioRxiv · 10.1101/010652

Interplay of TGFb superfamily members governs optic fissure closure

Stephan Heermann·Priska Eckert·Juan L Mateo·Eleni Roussa·Belal Rahhal·Aimee Zuniga·Kerstin Krieglstein·Joachim Wittbrodt

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Abstract

The optic fissure is a gap in the developing vertebrate eye and must be closed as development proceeds. A persisting optic fissure is referred to as coloboma, a major cause for blindness in children. Multiple factors have been linked to coloboma formation, however, the actual process of fissure closure is only poorly understood.\n\nBased on our findings we propose an important role of TGFb signaling for optic fissure closure. We show active TGFb signaling in the fissure margins, analyzed by a new TGFb signaling reporter zebrafish. We found BMP antagonists regulated by TGFb. These antagonists we also found expressed in the fissure margins. Finally we show a coloboma phenotype in a TGFb KO mouse. Microarray data analysis indicates intense TGFb dependent remodeling of the extracellular matrix (ECM) during optic fissure closure.\n\nWe propose that TGFb is driving optic fissure closure by ECM remodeling. As previously shown, inhibition of BMP signaling is important for such TGFb dependent ECM remodeling. We show that this is achieved by the regulation of BMP antagonists, expressed in the optic fissure margins.

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Stephan Heermann, Priska Eckert, Juan L Mateo, Eleni Roussa, Belal Rahhal, Aimee Zuniga, Kerstin Krieglstein, Joachim Wittbrodt. 2014-10-24. Interplay of TGFb superfamily members governs optic fissure closure. https://doi.org/10.1101/010652

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