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Journal of Neuroscience, Vol 15, 2575-2591, Copyright © 1995 by Society for Neuroscience
Developmental kinetics of GAD family mRNAs parallel neurogenesis in the rat spinal cord
R Somogyi, X Wen, W Ma and JL Barker
Laboratory of Neurophysiology, NINDS, NIH, Bethesda, Maryland 20892, USA.
GABA (gamma-amino butyric acid), a fast-acting synaptic transmitter in the
mature CNS, is synthesized from glutamate by GAD (glutamic acid
decarboxylase). We have developed an ultrasensitive PCR technique to
quantify the expression of GAD-related mRNAs during the development of the
rat cervical spinal cord and have localized them using in situ
hybridization. GAD65, GAD67, and an alternatively spliced variant of GAD67,
EP10, were quantified each day from embryonic (E) day 11 through E21, and
at postnatal days 0, 7, 14, and adult. GAD65 and GAD67 mRNAs were detected
at E11 and increased exponentially over three orders of magnitude during
embryonic development, then declined approximately threefold in the first-2
postnatal weeks. While the exponential growth phase coincided with the
progressive appearance of GAD67 in situ signals in both the ventral and
dorsal cord, the postnatal decline coincided with the virtual disappearance
of expression in the ventral region. EP10 expression was prominent in the
embryo, then declined markedly together with the mRNA encoding the
neuroepithelial stem cell marker, nestin. The concerted appearance of
GAD-related mRNAs paralleled transcripts encoding neuronal markers (light
and heavy neurofilaments) and also closely correlated with the expression
of GABA, mRNAs encoding GABAA receptor subunits, and depolarizing responses
to GABA. We have used the results on GAD-related mRNA expressions to
formulate a simple, minimal mathematical model that accounts for their
kinetics in terms of positive and negative feedback loops.
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