Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain

Bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. A review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders.Our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development.Proper forebrain patterning and cell-fate specification lay the foundation for complex behaviors. These neurodevelopmental events in large part depend on a series of gene expression refinements (reviewed in [1]) that commit cells to express certain phenotypic features that define circuit formation. Relatively subtle disturbances in development may underlie the etiology of neurodevelopmental disorders, especially when alternative cognitive phenotypes do not have an apparent malformation at the gross anatomical level. In the forebrain, cells producing γ-aminobutyric acid (GABAergic interneurons) have been implicated in neurodevelopmental disorders, including autism and schizophrenia [2-4]. These neurons are composed of a diverse class of cells providing a wide range of control of neural activity, and vary in neuroanatomical location, electrophysiological properties, transcriptome/proteome and innervation patterns as either local circuit or long-range projection neurons [5]. As with other cell types, the diversity of GABAergic neurons has its basis in different developmental origins, with timing and location of birth playing key roles in cell fate [1,6-8].Despite the phenotypic variety of GABAergic neurons, all use GABA as a neurotransmitter. In mammals, GABA is produced by one of two GABA-synthesizing enzymes, glutamic acid decarboxylase (GAD)65 or GAD67. These closely related enzymes are orthologs of the Caenorhabditis elegans protein UNC-25, which is found only in cells that produce GABA. Because UNC-25/GAD and other components