Cerebral Cortex Advance Access published online on December 5, 2006
Cerebral Cortex, doi:10.1093/cercor/bhl118
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Genetic Analysis of Anterior–Posterior Expression Gradients in the Developing Mammalian Forebrain
1 Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA, 2 Institute of Molecular Medicine, Department of Medicine, University of California at San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0613, USA, 3 Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA, 4 Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA and Program in Neurobehavioral Genetics, and Center for Autism Research, Semel Institute for Neuroscience and Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
Address correspondence to Dr Daniel H. Geschwind, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. Email: dhg{at}ucla.edu.
Intrinsic regulatory factors play critical roles in early cortical patterning, including the development of the anteroposterior (A-P) axis. To identify genes that are differentially expressed along the A-P axis of the developing cerebral cortex, we analyzed gene expression in presumptive frontal, parietal, and occipital cerebral walls of E12.5 mouse using complementary DNA microarrays. We identified 106 genes, including expressed sequence tags (ESTs), expressed in an A-P gradient in the embryonic brain and screened 88 by in situ hybridization for confirmation. Central nervous system (CNS) expression patterns of many of these genes were previously unknown. Others, such as Sfrp1, CoupTF1, and FABP7, were expressed in a manner consistent with previous studies, providing independent confirmation. Two related transcription factors, previously not implicated in CNS development, Fhl1 and Fhl2, were observed to be enriched in posterior and anterior telencephalon, respectively. We studied patterning gradients in Fhl1 knockout mice but observed no changes in gene expression related to A-P regionalization in the Fhl1 knockout mice. These data provide an important set of new candidates for studies of cortical patterning and maturation.
Key Words: cortical development • Fhl1 • Fhl2 • gene expression • microarray • protomap
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