Author:
Allen Wesley,Beckett Nathan,Brenchley Emma,Jung Sion,Wengler Jacob,Hall Lauren,Winn Cailey,Mann Meredith,May Rachel,Stark Michael,Mizrachi Dario
Abstract
Tight junctions (TJ) play a major role in the formation of various embryonic structures, including the neural tube. Disruptions of claudins (CLDN), a family of proteins critical to the TJ function, has been shown to induce neural tube defects (NTD) in chicken embryos. Clostridium perfringens enterotoxin (CPE) induces NTDs through this mechanism as it inhibits CLDNs 3, 4, 6, 7, 8, 9, 14, and 19, creating a pore in the TJ and causing cell death. CPE broadly targets these CLDNs in a nonspecific manner. Our research utilizes chimeric-claudin (chCLDN) proteins to target individual CLDN interactions, increasing understanding of their specific contributions to NTDs. Using chicken embryos, we have evaluated the role of chCLDN3 when compared to CPE and solvent. Gallus gallus chCLDN-3 (GG3) induced NTDs in chicken embryos at a significantly higher rate than negative controls and statistically similar rate to CPE, our positive control. Additionally, GG3 exhibited different NTD patterns from CPE, allowing us to investigate the unique contributions of CLDN3 in NTD formation and establish the value of this research method.