Cell Adhesion in Mouse Development (Marc Stemmler)
Classical cadherins and their molecular function during development and differentiation – Marc Stemmler
Cadherin-mediated adhesion is crucial during development and is deregulated during tumor progression. Despite our detailed knowledge about the Cadherins, including the similarities between E-cadherin (E-cad) and N-cadherin (N-cad) in sequence, structure and function, their unique properties in providing different cellular phenotypes is poorly understood. We aim to get insights into the molecular features and interactions of E-cad and N-cad leading to distinct cellular responses during important morphogenetic events. We use a gene replacement strategy to replace E-cad with N-cad and with sequences of chimeric cadherins to analyze their effect on development. In addition, we focus on unraveling the regulation of E-cad gene that is tightly controlled during development and requires sequences in intron 2.
We are analyzing cis-regulatory elements and transcription factors that mediate E-cad gene activation. The analysis will extend our knowledge about the role of cadherins during normal development as well as about their implication in tumor formation and metastasis. We aim to better understand the mechanisms of cadherin locus control to prevent deregulated gene expression required for invasion.