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.
Highlights
Gastrulation is a fundamental morphogenetic event that requires polarised cell behaviours for coordinated asymmetric cell movements
Dvl occupies a key position in the Wnt or planar cell polarity (Wnt/PCP) pathway to regulate the activation of downstream effectors during asymmetric cell movements
Our results strongly suggest a functional interaction between Lurap[1] and Dvl, which acts upstream of Jun N-terminal kinase (JNK) to modulate Wnt/PCP signalling during convergence and extension (CE) movements (Fig. 9e)
Summary
Gastrulation is a fundamental morphogenetic event that requires polarised cell behaviours for coordinated asymmetric cell movements. We report that Lurap[1] is a Dishevelled-interacting protein that regulates Wnt/PCP signalling in convergence and extension movements during vertebrate gastrulation. Time-lapse analyses indicate that Lurap[1], Dishevelled, and JNK functionally interact to orchestrate polarised cellular protrusive activity, and Lurap[1] is required for coordinated centriole/MTOC positioning in movement cells. Dvl occupies a key position in the Wnt/PCP pathway to regulate the activation of downstream effectors during asymmetric cell movements It contains three highly conserved functional domains known as DIX, PDZ, and DEP, which are implicated in specific interaction with different partners, leading to distinct signalling outcomes[32,33,34]. This protein is highly conserved among vertebrate species, its implication in regulating cell movements during early development has never been reported
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