title: Regulation of Schwann cell differentiation and proliferation by the Pax-3 transcription factor.
abstract: Pax-3 is a paired domain transcription factor that plays many roles during vertebrate development. In the Schwann cell lineage, Pax-3 is expressed at an early stage in Schwann cells precursors of the embryonic nerve, is maintained in the nonmyelinating cells of the adult nerve, and is upregulated in Schwann cells after peripheral nerve injury. Consistent with this expression pattern, Pax-3 has previously been shown to play a role in repressing the expression of the myelin basic protein gene in Schwann cells. We have studied the role of Pax-3 in Schwann cells and have found that it controls not only the regulation of cell differentiation but also the survival and proliferation of Schwann cells. Pax-3 expression blocks both the induction of Oct-6 and Krox-20 (K20) by cyclic AMP and completely inhibits the ability of K20, the physiological regulator of myelination in the peripheral nervous system, to induce myelin gene expression in Schwann cells. In contrast to other inhibitors of myelination, we find that Pax-3 represses myelin gene expression in a c-Jun-independent manner. In addition to this, we find that Pax-3 expression alone is sufficient to inhibit the induction of apoptosis by TGFβ1 in Schwann cells. Expression of Pax-3 is also sufficient to induce the proliferation of Schwann cells in the absence of added growth factors and to reverse K20-induced exit from the cell cycle. These findings indicate new roles for the Pax-3 transcription factor in controlling the differentiation and proliferation of Schwann cells during development and after peripheral nerve injury.
authors.affiliation: Peninsula College of Medicine and Dentistry, University of Exeter, Plymouth, Devon, United Kingdom.
authors.forename: Robin D S
authors.initials: RD
authors.lastname: Doddrell
authors.forename: Xin-Peng
authors.initials: XP
authors.lastname: Dun
authors.forename: Roy M
authors.initials: RM
authors.lastname: Moate
authors.forename: Kristjan R
authors.initials: KR
authors.lastname: Jessen
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.forename: David B
authors.initials: DB
authors.lastname: Parkinson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001917:Brachial Plexus / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism
chemical_list: D051767:Early Growth Response Protein 2; C497328:Egr2 protein, rat; D008565:Membrane Proteins; D000072041:PAX3 Transcription Factor; C530820:PAX3 protein, rat; D051761:Paired Box Transcription Factors; D016755:Proto-Oncogene Proteins c-jun; C086745:periaxin; D050816:Octamer Transcription Factor-6