Leucine repeat adaptor protein 1 interacts with Dishevelled to regulate gastrulation cell movements in zebrafish

Abstract

Gastrulation is a fundamental morphogenetic event that requires polarised cell behaviours for coordinated asymmetric cell movements. Wnt/PCP signalling plays a critical role in this process. Dishevelled is an important conserved scaffold protein that relays Wnt/PCP signals from membrane receptors to the modulation of cytoskeleton organisation. However, it remains unclear how its activity is regulated for the activation of downstream effectors. Here, we report that Lurap1 is a Dishevelled-interacting protein that regulates Wnt/PCP signalling in convergence and extension movements during vertebrate gastrulation. Its loss-of-function leads to enhanced Dishevelled membrane localisation and increased JNK activity. In maternal-zygotic lurap1 mutant zebrafish embryos, cell polarity and directional movement are disrupted. Time-lapse analyses indicate that Lurap1, Dishevelled, and JNK functionally interact to orchestrate polarised cellular protrusive activity, and Lurap1 is required for coordinated centriole/MTOC positioning in movement cells. These findings demonstrate that Lurap1 functions to regulate cellular polarisation and motile behaviours during gastrulation movements.