MMP14 Regulates Cranial Neural Crest Epithelial-to-Mesenchymal Transition and Migration

Abstract

Background: Neural crest is a vertebrate specific cell population. Induced at lateral borders of the neural plate, neural crest cells (NCCs) subsequently undergo epithelial-to-mesenchymal transition (EMT) to detach from the neuroepithelium before migrating into various locations in the embryo. Despite the wealth of knowledge of transcription factors involved in this process, little is known about the effectors that directly regulate neural crest EMT and migration. Results: Here, we examined the activity of matrix metalloproteinase MMP14 in NCCs and found that MMP14 is expressed in both premigratory and migrating NCCs. Overexpression of MMP14 led to premature migration of NCCs, while down-regulation of MMP14 resulted in reduced neural crest migration. Transplantation experiment further showed that MMP14 is required in NCCs, whereas MMP2, which can be activated by MMP14, is required in the surrounding mesenchyme. in vitro explant culture showed that MMP14 is required for neural crest EMT but not for spreading. This is possibly mediated by the changes in cadherin levels, as decreasing MMP14 level led to increased cadherin expression and increasing MMP14 level led to reduced cadherin expression. Conclusions: The results demonstrate that MMP14 is critical for neural crest EMT and migration, partially through regulating the levels of cadherins. Developmental Dynamics 247:1083-1092, 2018. © 2018 Wiley Periodicals, Inc.