Mechanisms of Limb Development
We are interested in basic mechanisms of limb development and how they relate to abnormal development as they are observed in human limb malformations. Limb development is normally governed by a four-dimensional signalling network that directs and controls cell identity and differentiation within the limb. A disturbance of this intricate system by e.g. gene mutations or gene misexpression can result in a myriad of phenotypes including abnormal digit number (polydactyly/oligodactyly), fusion of digits (syndactyly), short or missing elements (brachydactyly), abnormalities of joint formation (synostoses), or abnormalities of dorsoventral patterning. Because of the easy accessibility of the limb, the process of normal and abnormal development can be observed and monitored in appropriate model systems. We investigate limb development in the mouse because signalling pathways and phenotype are highly similar to humans.
Limb development has been a paradigm to study gene regulatory networks and mechanisms of gene regulation. We are particularly interested in the genomic regulation of gene expression in the 3D space of the developing limb. This involves the function of enhancers and how they interact with their target promoters. An intricate part of this regulation lies in the 3D architecture of the genome and how it changes over time.