Although best known as an inhibitory neurotransmitter, intriguing evidence hasimplicated GABA as a key signaling molecule in craniofacial development in mammals.Glutamate is converted to GABA by an enzyme called glutamic acid decarboxylase(GAD), which exists in two isoforms, GAD67 and GAD65. The GAD1 and GAD2 genesencode these isoforms, respectively. A decrease in GAD activity in the human brain isoften associated with epilepsy, schizophrenia and related neurological disorders. In miceand humans, mutations in gad1, but not gad2, result in defects in palate development, andmutations in the Gabrb3 gene, which encodes the 3 subunit of the GABAA receptor,exhibit a comparable phenotype to gad1 mutations. These results suggest that GABAsignaling, through the GABAA receptor, can play an important and conserved role incraniofacial development. However, the mechanism of this process is not known andcannot be easily investigated in a mammalian system. In this work, translation-blockingmorpholinos against the GAD genes were used to alter expression within the larvalzebrafish. While gad2 morphants looked phenotypically normal, gad1 morphant animalsexhibited altered cranial structures at 1 and 7 dpf. Yet, both gad1 and gad2 morphantsexhibited spontaneous seizure-like neural activity. Through the use of photoactivatablecaged-morpholinos, the craniofacial deformities could be bypassed when photolysis wascarried out at 24 hpf. Electrophysiological recordings showed that while dark-raisedCyHQ-gad1 morphant animals looked phenotypically comparable to wild-type animals,they exhibited abnormal, seizure-like neural activity. These findings support the idea thatgad1 exhibits a novel function in craniofacial development, independent of its activity inGABA synthesis.