Collective cell movements termed convergent extension (CE) drive the elongation of tissues and organs in essentially all animals. In vertebrates, CE is controlled by the planar cell polarity (PCP) signaling system, and defects in PCP-dependent convergent extension are associated with human neural tube defects and skeletal dysplasias. We feel that the profound lack of information regarding the basic cell biology of CE as it occurs in vertebrate animals in vivo represents the key challenge in the field at this time. Building on our recent successes in advanced imaging and proteomics, this proposal takes a cell biological approach, focusing on fundamental cellular machines of cadherin adhesion, actin assembly, and the septin cytoskeleton and how they are deployed to drive PCP-mediated CE.
This study centers cell movements called convergent extension which are controlled by a set of proteins called the planar cell polarity (PCP) proteins. These experiments will be significant because convergent extension is essential for neural tube closure and limb morphogenesis, and failure of these movements results in a human birth defects such as neural tube defects and skeletal dysplasia. Thus, experiments proposed here will shed new light on mechanisms underlying human congenital anomalies.
