Seven pass Cadherins CELSR1-3.

Goffinet, André [UCL] Tissir, Fadel [UCL]

Cadherin EGF LAG seven-pass G-type receptors 1, 2 and 3 (CELSR1-3) form a family of three atypical cadherins with multiple functions in epithelia and in the nervous system. During the past decade, evidence has accumulated for a key role of CELSR1 in epithelial planar cell polarity (PCP), and for CELSR2 and CELSR3 in ciliogenesis and neural development, especially neuron migration and axon guidance in the central, peripheral and enteric nervous systems. Phenotypes in mutant mice indicate that CELSR proteins work in concert with FZD3 and FZD6, but several questions remain. Apart from PCP signaling pathways implicating CELSR1 that begin to be unraveled, little is known about other signals generated by CELSR2 and CELSR3. A crucial question concerns the putative ligands that trigger signaling, in particular what is the role of WNT factors. Another critical issue is the identification of novel intracellular pathways and effectors that relay and transmit signals in receptive cells? Answers to those questions should further our understanding of the role of those important molecules not only in development but also in regeneration and disease.