Gene Expression Profiling of Preplate Neurons Destined for the Subplate: Genes Involved in Transcription, Axon Extension, Neurotransmitter Regulation, Steroid Hormone Signaling, and Neuronal Survival


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Abstract

During mammalian corticogenesis a series of transient cell layers establish laminar architectonics. The preplate, which forms from the earliest-generated neurons, separates into the marginal zone and subplate layer. To provide a systematic screen for genes involved in subplate development and function, we screened lines of transgenic mice, generated using bacterial artificial chromosome methodology (GENSAT Project), to identify transgenic lines of mice that express the enhanced green fluorescent protein (EGFP) reporter in preplate neurons destined for the subplate. Gene expression profiling of RNA purified from EGFP-positive neurons identified over 200 genes with enriched expression in future subplate neurons. Major classes of subplate-enriched genes included genes involved in transcriptional processes, cortical development, cell and axon motility, protein trafficking and steroid hormone signaling. Additionally, we identified 10 genes related to degenerative diseases of the cerebral and cerebellar cortex. Cre recombinase–based fate mapping of cells expressing Phosphodiesterase 1c (Pde1c) revealed beta-galactosidase positive cells in the ventricular zone, as well as the subplate, suggesting that subplate neurons and cortical projection neurons may be derived from common progenitors. These experiments therefore reveal genetic markers, which identify subplate neurons from the earliest stages of their development, and genes with enriched expression in subplate neurons during early stages of corticogenesis.

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