An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

摘要: The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos found a previously unknown, evolutionarily recent function this ancient protein. that htt was essential homotypic interactions between neuroepithelial cells; it permitted rosette formation by regulating metalloprotease ADAM10 activity Ncadherin cleavage. This embedded the N terminus of phenocopied treatment knockdown with an inhibitor. Notably, cells, reversion rosetteless phenotype occurred only expression heterologues from deuterostome organisms. Conversely, all we tested, including Drosophila melanogaster Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one htt’s ancestral function(s), but, deuterostomes, evolved to acquire unique regulatory controlling adhesion via ADAM10-Ncadherin, implications brain evolution development.