Osheroff screened these genes for involvement in the earliest stages of brain development, when the first neurons begin to stratify across six layers that form the scaffolding of the embryonic brain inside a folding neural tube. Using fluorescence-activated cell sorting, Osheroff isolated the neurons destined for the layer known as the subplate from the Cajal-Retzius neurons, which carry on beyond the subplate to the layer known as the marginal zone. She identified 229 genes specifically dedicated to developing the subplate neurons and found that they were involved in a broad range of activities including cortical development, cell and axon motility, protein trafficking, steroid hormone signaling and central nervous system degenerative diseases.

The work indicates the breadth of factors involved in the early development of neurons and provides investigators with a biochemical handle to start investigating the various contributions, says Hatten. "It's a roadmap, not an answer," she says. "These results could really change the direction of research."

Cerebral Cortex online: April 27, 2009: Gene Expression Profiling of Preplate Neurons Destined for the Subplate: Genes Involved in Transcription, Axon Extension, Neurotransmitter Regulation, Steroid Hormone Signaling, and Neuronal Survival Hilleary Osheroff and Mary E. Hatten

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