Journal Article

Mutational analysis of dishevelled genes in zebrafish reveals distinct functions in embryonic patterning and gastrulation cell movements

Li, Yu-Long, Shao, Ming, Shi, De-Li, Saquet, Audrey, Xing, Yan-Yi, Zhang, Chong, Liu, Yuan-Yuan, Cheng, Xiao-Ning

2018

Overview

Wnt signaling plays critical roles in dorsoventral fate specification and anteroposterior patterning, as well as in morphogenetic cell movements. Dishevelled proteins, or Dvls, mediate the activation of Wnt/ß-catenin and Wnt/planar cell polarity pathways. There are at least three highly conserved Dvl proteins in vertebrates, but the implication of each Dvl in key early developmental processes remains poorly understood. In this study, we use genome-editing approach to generate different combinations of maternal and zygotic dvl mutants in zebrafish, and examine their functions during early development. Maternal transcripts for dvl2 and dvl3a are most abundantly expressed, whereas the transcript levels of other dvl genes are negligible. Phenotypic and molecular analyses show that early dorsal fate specification is not affected in maternal and zygotic dvl2 and dvl3a double mutants, suggesting that the two proteins may be dispensable for the activation of maternal Wnt/ß-catenin signaling. Interestingly, convergence and extension movements and anteroposterior patterning require both maternal and the zygotic functions of Dvl2 and Dvl3a, but these processes are more sensitive to Dvl2 dosage. Zygotic dvl2 and dvl3a double mutants display mild axis extension defect with correct anteroposterior patterning. However, maternal and zygotic double mutants exhibit most strongly impaired convergence and extension movements, severe trunk and posterior deficiencies, and frequent occurrence of cyclopia and craniofacial defects. Our results suggest that Dvl2 and Dvl3a products are required for the activation of zygotic Wnt/ß-catenin signaling and Wnt/planar cell polarity pathway, and regulate zygotic developmental processes in a dosage-dependent manner. This work provides insight into the mechanisms of Dvl-mediated Wnt signaling pathways during early vertebrate development.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Catenin / Convergence / Danio rerio / Dishevelled protein / Embryo / Embryogenesis / Embryos / Gastrulation / Gene expression / Gene mutation / Gene mutations / Genetic aspects / Genetic research / Genomes / Kinases / Laboratories / Life Sciences / Pattern formation / Polarity / Proteins / Research and Analysis Methods / Signal transduction / Transcription / Wnt protein