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Nat Commun
2017 Nov 07;81:1353. doi: 10.1038/s41467-017-01552-x.
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Leucine repeat adaptor protein 1 interacts with Dishevelled to regulate gastrulation cell movements in zebrafish.
Cheng XN
,
Shao M
,
Li JT
,
Wang YF
,
Qi J
,
Xu ZG
,
Shi DL
.
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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.
Fig. 7. Overexpression of Lurap1 impairs CE movements and notochord cell polarity. a–f In situ hybridisation analysis using dlx3 (a–c) and ntla (d–f) to reflect the extent of neural plate convergence and axial mesoderm extension in zebrafish embryos. Overexpression of Lurap1 potently affects CE movements, while Lurap1ΔC shows a weak effect. g–i Analysis by confocal microscopy of notochord width and cell shape in indicated conditions. Representative images are shown, with statistical numbers of embryos scored from three independent experiments. j, k Graphs show the statistics of cell shape (LWR) and orientation of notochord cells in uninjected, and lurap1 or lurap1ΔC-injected embryos. Bars represent the mean values ± s.d. and the data were calculated using 20 cells randomly selected in a representative image for each condition (***P < 0.001; NS, not significant; Student’s t-test). l–n Live images of normal and CE defective Xenopus embryos at tail-bud stage. o Statistical analysis of the dose-dependent CE defects following overexpression of Lurap1 or Lurap1ΔC. The colour codes for different categories of phenotypes are indicated in the live images on the left. The data were scored from four experiments using different batches of embryos, with total number of embryos shown on the top of each stacked column. Xdd1 was included in the analysis for a comparison. Scale bars: a–f 200 µm; g–i 20 µm; l–n 1.2 mm
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