Tight junction membrane protein's role in neural tube defects

Abstract

More than 300,000 infants worldwide are born with neural tube defects (NTD), making it the second most common birth defect in the world. Many genetic and environmental factors have been identified as drivers of NTDs, some of which have been tied to damage of tight junctions (TJ), which are critical for the success of neural tube folding. Claudins (CLDN), occludin (OCLN) and junctional adhesion molecules (JAMs) are essential components of the TJ and are key players in its function. In the chicken embryo, clostridium perfringens enterotoxin (CPE) induces NTDs, by interacting broadly with CLDN3, ‐4, and ‐8. These interactions increase TJ permeability to an influx of calcium ions, causing cell death. There is no information for the role of OCLN or JAMs in NTDs. Our laboratory has created Synthetic Biology approaches to produce soluble CLDNs, OCLN and JAMs. These are detergent independent proteins that result in molecules that retain structure and adhesive properties of the native membrane protein. We present evidence that specific interactions, rather than the broad specificity of CPE, can be used to identify specific mechanisms leading to NTD formation. Our approach expands to the role of OCLN and JAMs in the formation of NTDs. These new tools may be used in developmental research as an alternative for genetic manipulation with equal value.