;MITHSONIAN SCI  NCE  lNFORMATlON           U.S. DEPARTMENT OF       PROJECT NUMBER
`RDJECT NUMBER  Do NOT use this space   HEALTH EDUCATION AND WELFARE
            PGBLI~OCH;$~T~SERVICE     ZOl HL 00011-02 LBG
                          INTAAYURAL RESEARCH PROJECT

                                I                           I
PERIOD COVERED

July 1, 1976 through September 30, 1977
TITLE OF PROJECT (80 characters or less)

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

COOPERATING UNITS (if any)

LAB/BRANCH
Laboratory of Biochemical Genetics
5;                   :.
Section on Molecular Biology
INSTITUTE AND LOCATION
NHLBI, NIH, Bethesda, Maryland 20014
TOTAL MANYEARS:             PROFESSIONAL:
0.5                0.5

OTHER:

CHECK APPROPRIATE BOX(ES)                                 I
`3 (a) HUMAN SUBJECTS        O (b) HUMAN TISSUES        [x (c) NEITHER

fl (al) MINORS 0 (a2) INTERVIEWS

SUMMARY OF WORK (200 words or less - underline keywords)

    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
                                                               -v
~ cultures.  3) The presence of GABA in the culture medium prevented the
1  development of glutamic acid decarboxylase activity in aggregate cultures.
~ 1 4 The proposed course of this project is to attempt to correlate the
biochemical changes observed, with synaptogenesis in the retina.

c
PHS-6040

(Rev. 1 o-76)


Project Description:

Z01 HL 00011-02 LBG

   Objectives:  The objective of the project is to study the biochemical
step required for synaptogenesis in chick embryo retina.

   Major Findings:  Two pathways for y-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 y-aminobutyric a&d.  The second route of synthesis is dependent upon the
conversion of glutamic acid to y-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 decar-
boxylase 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.