Abstract
Neural crest (NC) cells are multipotent embryonic cells that form melanocytes, craniofacial bone and cartilage, and the peripheral nervous system in vertebrates. NC cells express many cadherin proteins, which control their specification, epithelial to mesenchymal transition (EMT), migration, and mesenchymal to epithelial transition. Abnormal NC development leads to congenital defects including craniofacial clefts as well as NC-derived cancers. Here, we identify the role of the type II cadherin protein, Cadherin-11 (CDH11), in early chicken NC development. CDH11 is known to play a role in NC cell migration in amphibian embryos as well as cell survival, proliferation, and migration in cancer cells. It has also been linked to the complex neurocristopathy disorder, Elsahy-Waters Syndrome, in humans. In this study, we knocked down CDH11 translation at the onset of its expression in the NC domain during NC induction. Loss of CDH11 led to a reduction of bonafide NC cells in the dorsal neural tube combined with defects in cell survival and migration. Loss of CDH11 increased p53-mediated programmed-cell death, and blocking the p53 pathway rescued the NC phenotype. Our findings reveal an early requirement for CDH11 in NC development and demonstrated the complexity of the mechanisms that regulate NC development, where a single cell-cell adhesion protein simultaneous controls multiple essential cellular functions to ensure proper specification, survival, and transition to a migratory phase in the dorsal neural tube. Our findings may also increase our understanding of early cadherin-related NC developmental defects.
Highlights
Cadherin proteins are calcium dependent cell-cell adhesion molecules, which are essential for the development and maintenance of embryonic tissues (Giger and David, 2017; Taneyhill and Schiffmacher, 2017)
CDH11 function has been extensively examined during neural crest (NC) migration and epithelial to mesenchymal transition (EMT) in amphibian embryos (Hadeball et al, 1998; Vallin et al, 1998; Borchers et al, 2001; Kashef et al, 2009; McCusker et al, 2009; Koehler et al, 2013; Abbruzzese et al, 2016), but less is known about its endogenous expression and role in amniotes, which encouraged us to begin by examining the spatiotemporal expression pattern of the CDH11 protein in the chicken embryo
Loss of CDH11 reduced the number of specified cells (SNAI2, SOX9, SOX10-positive) that normally proceed to cell migration and reduced proteins that are crucial for NC cell survival (SNAI2, SOX9)
Summary
Cadherin proteins are calcium dependent cell-cell adhesion molecules, which are essential for the development and maintenance of embryonic tissues (Giger and David, 2017; Taneyhill and Schiffmacher, 2017). Cadherin 11 (Osteoblast-cadherin/CDH11), and Cadherin-6B (CDH6), which have been linked to CNS patterning, NC cell delamination, EMT, and migration during embryonic development (Taneyhill et al, 2007; Liu et al, 2008; Kashef et al, 2009; Schiffmacher et al, 2014, 2016). With varied timing and onset of protein expression, the regulation and function of cadherin proteins is clearly important for normal development of the CNS, NC cells, and NC derivatives
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