FACS-array gene expression analysis during early development of mouse telencephalic interneurons.
Cortical interneuron dysfunction has been implicated in multiple human disorders including forms of epilepsy, mental retardation, and autism. Although significant advances have been made, understanding the biologic basis of these disorders will require a level of anatomic, molecular, and genetic detail of interneuron development that currently does not exist. To further delineate the pathways modulating interneuron development we performed fluorescent activated cell sorting (FACs) on genetically engineered mouse embryos that selectively express green fluorescent protein (GFP) in developing interneurons followed by whole genome microarray expression profiling on the isolated cells. Bioinformatics analysis revealed expression of both predicted and unexpected genes in developing cortical interneurons. Two unanticipated pathways discovered to be up regulated prior to interneurons differentiating in the cortex were ion channels/neurotransmitters and synaptic/vesicular related genes. A significant association of neurological disease related genes to the population of developing interneurons was found. These results have defined new and potentially important data on gene expression changes during the development of cortical interneurons. In addition, these data can be mined to uncover numerous novel genes involved in the generation of interneurons and may suggest genes/pathways potentially involved in a number of human neurological disorders.
Marsh
Eric D
ED
Division of Neurology, Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia 19130, USA. marshe@email.chop.edu
Minarcik
Jennifer
J
Campbell
Kenneth
K
Brooks-Kayal
Amy R
AR
Golden
Jeffrey A
JA
D000818:Animals; D002465:Cell Movement; D019295:Computational Biology; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D013687:Telencephalon / Q000196:embryology*
D049452:Green Fluorescent Proteins