Regulation of Digit Patterning and Chondrogenesis by BMP Antagonists

• Applicant: Dr. Robert Reinhardt
• Subject Area: Developmental Biology ; Evolutionary Cell and Developmental Biology (Zoology) ; Cell Biology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317038184

The growth and patterning of extremities depends on integration of signals by progenitor cells. Mutations in these signaling networks and downstream effectors underlie various human congenital limb malformations. The relevant gene regulatory networks have been identified, but analysis of the functionally relevant spatio-temporal interactions is still a matter of intense research. Therefore, the major aim of this project is to gain insight into how antagonists of Bone Morphogenetic Proteins (BMPs) modulate signaling during digit patterning and chondrogenesis using the mouse embryo as model. BMP signaling is required to induce formation of the cartilage primordia of the future digits and subsequently during progression of chondrogenesis and endochondral ossification. It has been shown in a large number of different contexts that BMP activity is tightly regulated by specific interactions of ligands with different extra-cellular BMP antagonists such as Gremlin1 and Noggin. The host group has obtained evidence that BMP-antagonist interactions control the balance of proliferative expansion and the onset of differentiation of chondrogenic progenitors. I will investigate the molecular and cellular mechanisms by which regulation of BMP signaling by antagonists controls the fate and differentiation of the digit precursors that give rise to cartilage and bone.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Rolf Zeller