Temporal and spatial expression of glutamic acid decarboxylases in human fetal brain

The expression of two isoforms of glutamic acid decarboxylase, GAD67 and GAD65, was analyzed in central nervous system (CNS) tissues obtained from normal second trimester human fetuses after elective termination of pregnancy. After RT-PCR amplification of sequences contained in total RNA extracts, Southern blotting indicated that GAD67 and GAD65 mRNAs can be detected in frontal pole tissue as early as the 12th week of gestation (12 GW). GAD67 message is strongly expressed during early second trimester and decreases slightly thereafter but remains abundant. In contrast, GAD65 message decreases rapidly and becomes undetectable by the 19 GW. However, GAD67 and GAD65 are similar in their spatial expression in the CNS at 22 GW. GAD67 and GAD65 messages are highly expressed in the cerebellum but expressed in low levels, if at all, in the spinal cord during this gestational period. These results suggest that GAD67 may have a greater role in neuron differentiation than GAD65 during human brain development.