title: The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.
abstract: During vertebrate neurulation, cranial neural crest cells (CNCCs) undergo epithelial to mesenchymal transition (EMT), delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL) receptor-related protein 5 (Lrp5) plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore; Centre for Bioimaging Sciences (CBIS), National University of Singapore, Singapore, Singapore.
authors.forename: Bernd
authors.initials: B
authors.lastname: Willems
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore; Centre for Bioimaging Sciences (CBIS), National University of Singapore, Singapore, Singapore.
authors.forename: Shijie
authors.initials: S
authors.lastname: Tao
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore; Centre for Bioimaging Sciences (CBIS), National University of Singapore, Singapore, Singapore.
authors.forename: Tingsheng
authors.initials: T
authors.lastname: Yu
authors.affiliation: Biology Department, Ghent University, Ghent, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Huysseune
authors.affiliation: Biology Department, Ghent University, Ghent, Belgium.
authors.forename: Paul Eckhard
authors.initials: PE
authors.lastname: Witten
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore; Centre for Bioimaging Sciences (CBIS), National University of Singapore, Singapore, Singapore.
authors.forename: Christoph
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012886:Skull / Q000166:cytology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5; D029961:Zebrafish Proteins