TY - JOUR T1 - Interplay of TGFb superfamily members governs optic fissure closure JF - bioRxiv DO - 10.1101/010652 SP - 010652 AU - Stephan Heermann AU - Priska Eckert AU - Juan L. Mateo AU - Eleni Roussa AU - Belal Rahhal AU - Aimee Zuniga AU - Kerstin Krieglstein AU - Jochim Wittbrodt Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/10/24/010652.abstract N2 - 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.Based 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.We 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. ER -