The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development.
The genetic hierarchy that controls myelination of peripheral nerves by Schwann cells includes the POU domain Oct-6/Scip/Tst-1and the zinc-finger Krox-20/Egr2 transcription factors. These pivotal transcription factors act to control the onset of myelination during development and tissue regeneration in adults following damage. In this report we demonstrate the involvement of a third transcription factor, the POU domain factor Brn-2. We show that Schwann cells express Brn-2 in a developmental profile similar to that of Oct-6 and that Brn-2 gene activation does not depend on Oct-6. Overexpression of Brn-2 in Oct-6-deficient Schwann cells, under control of the Oct-6 Schwann cell enhancer (SCE), results in partial rescue of the developmental delay phenotype, whereas compound disruption of both Brn-2 and Oct-6 results in a much more severe phenotype. Together these data strongly indicate that Brn-2 function largely overlaps with that of Oct-6 in driving the transition from promyelinating to myelinating Schwann cells.
Jaegle
Martine
M
Departments of Cell Biology and Genetics and Neurosciences, Erasmus University Medical Center, 3000DR Rotterdam, Netherlands.
Ghazvini
Mehrnaz
M
Mandemakers
Wim
W
Piirsoo
Marko
M
Driegen
Siska
S
Levavasseur
Francoise
F
Raghoenath
Smiriti
S
Grosveld
Frank
F
Meijer
Dies
D
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic; D005091:Exons; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009186:Myelin Sheath / Q000502:physiology; D050816:Octamer Transcription Factor-6; D050809:POU Domain Factors; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D012583:Schwann Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; C494180:Pou3f1 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors; C085076:transcription factor Brn-2; D050816:Octamer Transcription Factor-6