Embryonic Epithelial Development is Modulated by Extracellular Calcium

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Title: Embryonic Epithelial Development is Modulated by Extracellular Calcium
Author: Mack, Cina Marie
Advisors: Dr. Betty L. Black, Committee Co-Chair
Dr. Russell Borski, Committee Co-Chair
Dr. Robert Argenzio, Committee Member
Dr. Herbert Underwood, Committee Member
Abstract: This study investigated the effects of calcium on epithelial differentiation in organ-cultured embryonic chick duodenum. Alteration of calcium ion concentration of culture medium above or below the physiological Ca2+ concentration of embryonic chick serum strongly influenced gastrointestinal development. Culture of 16- or 18-day embryonic intestine in high Ca2+ resulted in elevated activity of alkaline phosphatase, a brush border digestive enzyme, and an increase in goblet cell number within the epithelium. Conversely, low Ca2+ reduced both indices of functional differentiation. Lead acetate, a disruptor of Ca2+ homeostasis, was as effective as low Ca2+ in impeding epithelial differentiation. The voltage sensitive Ca2+-channel (VSCC) antagonists verapamil and nifedipine were used to selectively block Ca2+ influx into the cultured tissue. Both verapamil, a non-specific channel blocker, and nifedipine, which is highly selective for L-type VSCCs, significantly inhibited differentiation, but nifedipine gave more consistent results. Imaging of calcium within the epithelium of cultures was performed by confocal scanning laser microscopy, using the fluorescent calcium probe indo-1. Quantification of Ca2+ within enterocytes revealed that both verapamil and nifedipine reduced intracellular Ca2+ concentration. Together, these results indicate that extracellular Ca2+ influences epithelial differentiation by modulating intracellular Ca2+-dependent signaling pathways, possibly mediated by VSCCs.
Date: 2002-09-23
Degree: PhD
Discipline: Physiology
URI: http://www.lib.ncsu.edu/resolver/1840.16/3316


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