Project Number: Z01 HL 00011-02 LBG
Period Covered: July 1, 1976 through September 30, 1977
Title of Project: The Development of Chick Embryo Retina
Names, Laboratory and Institute Affiliations, and Titles of Principal Investigators and All Other Professional Personnel Engaged on the Project:
PI: F.G. De Mello, Visiting Associate, LBG NHLBI
Marshall Nirenberg, Chief, LBG, LBG NHLBI
Lab/Branch: Laboratory of Biochemical Genetics
Section:  Section on Molecular Biology
Institute and Location: NHLBI, NIH, Bethesda, Maryland 20014
Total Man Years: 0.5
Professional: 0.5
Summary of Work:
Some biochemical aspects of chick embryo retina differentiation were studied: 1) An alternate route for GABA synthesis was characterized in the retina; which depends upon the conversion of putrescine to GABA.  2) Glutamic acid decarboxylase specific activity in the retina, increased during the course of embryonic development, either when measured in ovo or in aggregate cultures.  3) The presence of GABA in the culture medium prevented the development of glutamic acid decarboxylase activity in aggregate cultures. 4) The proposed course of this project is to attempt to correlate the biochemical changes observed, with synaptogenesis in the retina.
Project Description:
Objectives:  The objective of the project is to study the biochemical step required for synaptogenesis in chick embryo retina.
Major Findings:  Two pathways for gamma-aminobutyric acid synthesis were found in chick embryo retina.  The first pathway depends upon the conversion of putrescine to ornithine decarboxylase and the subsequent conversion of ornithine to gamma-aminobutyric acid.  The second route of synthesis is dependent upon the conversion of glutamic acid to gamma-aminobutyric acid, catalyzed by glutamic acid decarboxylase.  Elevation of cAMP levels in neuroblastoma cells was shown to induce ornithine decarboxylase activity.  Thus, in the developing embryo, neurotransmitters which affect cAMP levels may regulate ornithine decarboxylase activity and thereby control the rate of GABA synthesis from ornithine.
GABA was found to regulate the specific activity of glutamic acid decarboxylase in cells dissociated from chick embryo retina and cultured in vitro.
Significance to Biomedical Research:  These findings show that GABA can be synthesized by a novel pathway and provide new insight on the relationship and regulation of GABA synthesis.
Proposed Course:  To determine the effect of retina neurotransmitters and other compounds on retina synaptogenesis.
Publications:
1. De Mello, F. G., Bachrach, U. and Nirenberg, M.:  Ornithine and glutamic acid decarboxylase activities in the developing retina.  J. Neurochem. 27: 847-851, 1976.