Domain-restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos

Glutamic acid decarboxylase (GAD) is the biosynthetic enzyme for gamma-amin obutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates. In addition to the adult CNS, GABA and GAD also have been detected in embryos, although their precise localizatio n and specific functions in embryonic development have not been elucidated. In this paper, the authors studied the cellular distribution of two GAD is oforms, GAD65 and GAD67, in midgestation mouse embryos by in situ hybridiza tion histochemistry. With few exceptions, it was found that GAD65 and GAD67 mRNAs are localized in overlapping cellular domains of the embryonic CNS t hat later develop into regions with a strong GABAergic contribution. The CA D-expressing cells are situated in the differentiating zone of the embryoni c day 10.5 (E10.5) through E11.5 CNS and in the subventricular zone and the mantle zone of the E12.5 CNS, which suggests that they are committed neuro nal precursors. By using a specific serum for GABA, a similar pattern of di stribution was obtained, indicating that GAD mRNAs are translated efficient ly into enzymatically active GAD, which produces embryonic GABA. The expres sion domains of GAD overlap with those of genes that are known to be involv ed in the patterning of the embryonic CNS. The two GAD mRNAs also are detec ted outside of the embryonic CNS in various cell types, mainly those of pla codal and neural crest origin. This pattern of expression is consistent wit h the notion that GAD and its product, GABA, play a signaling role during d evelopment. (C) 2000 Wiley-Liss, Inc.