Connexin 43 Function in the Cranial Neural Crest

Abstract

Connexins are transmembrane proteins that cluster to form intercellular channels called gap junctions, which function to allow direct diffusion of small molecules and ions between adjacent cells. Gap junctions are composed of two connexons (one on each cell which are docked head‐to‐head) consisting either of homomeric or heteromeric connexin proteins, although only certain combinations of connexins are possible. Connexin 43 is one of the predominant components of gap junctions and is expressed in multiple organisms and their tissues. To date, however, very little is known about the role of gap junctions, and specifically Connexin 43, in the neural crest. Immunohistochemical analyses revealed that Connexin 43 is expressed in premigratory cranial neural crest cells as well as during the epithelial‐to‐mesenchymal transition (EMT), migration, and coalescence of neural crest cells with placodal neurons as the trigeminal ganglion assembles. Interestingly, Connexin 43 is also observed in the cranial mesenchyme, but placodal neurons lack Connexin 43. Given the robust expression of Connexin 43 in the neural crest, we sought to elucidate the role of Connexin 43, and gap junctions in particular, during neural crest cell EMT and migration. To this end, we are assessing the presence of gap junctions in the neural crest and performing molecular and chemical perturbation experiments to alter Connexin 43 and general gap junction function. Our initial results reveal that gap junctions form between migratory neural crest cells generated from explants of premigratory neural crest tissue in an ex vivo culture assay. In future experiments, we will inhibit gap junctions using pharmacological reagents and modulate levels of Connexin 43 through knockdown and overexpression experiments, evaluating effects on neural crest cell EMT and migration in all approaches. Importantly, these assays will confirm that Connexin 43 is critical for gap junction function in neural crest cells. These data will provide insight into how neural crest cells interact and communicate during EMT and migration to allow for proper embryonic patterning throughout vertebrate development.Support or Funding InformationThis research was funded by ACS RSG‐1502301‐CSM and NIH R01DE024217 (L.A.T.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.