Experimental analysis of mechanisms of late neurulation in a model of embryonic zebrafish
Sin, Melvin Wai Loong
Date of Issue2015
School of Chemical and Biomedical Engineering
A*STAR Institute of Chemical and Engineering Science, IMCB
Chronic back pain is a common ailment experienced by many humans. One of the common causes is deficiency or impairment to neurulation, resulting in distension of the central canal. There is a wide range of range of diseases resulting from neural tube defects, causing a wide range of neurological complications, from as minor as numbness to as severe as paralysis or even fatality in neonatal. In this project, we used several transgenic Zebrafish ET lines to study the development of components of the neural tube, mainly the roof plate cells, central canal and floor plate cells. Based on this information, we used microinjections of various drugs into the hindbrain ventricle of embryos to disrupt the normal development of these components and model a distension of the central canal. Our findings show that Blebbistatin (inhibitor of myosin II), Y27632 (inhibitor of Rho-associated protein kinase), and Phalloidin (inhibitor of actin disassembly) disrupted the normal development of the neural tube via different mechanisms. Y27632 severs the attachment between roof plate cells and central canal via ROCK inhibition. Blebbistatin led to distension of the central canal due to loss of stiffness via myosin II inhibition. This phenotype observes closely mimics that of the clinical condition hydromyelia.