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The Journal of Neuroscience, December 1, 2002, 22(23):10217-10231

Identification of Genes That Are Downregulated in the Absence of the POU Domain Transcription Factor pou3f1 (Oct-6, Tst-1, SCIP) in Sciatic Nerve

John R. Bermingham Jr¹, Susan Shumas², Tom Whisenhunt³, Erich E. Sirkowski², Shawn O'Connell³, Steven S. Scherer², and Michael G. Rosenfeld³

¹ McLaughlin Research Institute, Great Falls, Montana 59405, ² Department of Neurology, University of Pennsylvania, Philadelphia Pennsylvania 19104-6077, and ³ Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0648

Despite the importance of myelinating Schwann cells in health and disease, little is known about the genetic mechanisms underlying their development. The POU domain transcription factor pou3f1 (Tst-1, SCIP, Oct-6) is required for the normal differentiation of myelinating Schwann cells, but its precise role requires identification of the genes that it regulates. Here we report the isolation of six genes whose expression is reduced in the absence of pou3f1. Only one of these genes, the fatty acid transport protein P₂, was known previously to be expressed in Schwann cells. The LIM domain proteins cysteine-rich protein-1 (CRP1) and CRP2 are expressed in sciatic nerve and induced by forskolin in cultured Schwann cells, but only CRP2 requires pou3f1 for normal expression. pou3f1 appears to require the claw paw gene product for activation of at least some of its downstream effector genes. Expression of the novel Schwann cell genes after nerve injury suggests that they are myelin related. One of the genes, tramdorin1, encodes a novel amino acid transport protein that is localized to paranodes and incisures. Our results suggest that pou3f1 functions to activate gene expression in the differentiation of myelinating Schwann cells.

Key words: myelin; pou3f1; Oct-6; Tst-1; SCIP; claw paw; Schwann cells; tramdorin; dendrin; CRP1; CRP2; P₂; representational difference analysis

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Copyright © 2002 Society for Neuroscience  0270-6474/02/222310217-15$05.00/0

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