A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration.
While an important role for the POU domain transcription factor Oct-6 in the developing peripheral nerve has been well established, studies into its exact role in nerve development and regeneration have been hampered by the high mortality rate of newborn Oct-6 mutant animals. In this study we have generated a Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this allele (deltaSCE allele) reveals that rate-limiting levels of Oct-6 in Schwann cells are dependent on the SCE and that this element does not contribute to Oct-6 regulation in other cell types. We demonstrate a Schwann cell autonomous function for Oct-6 during nerve development as well as in regenerating nerve. Additionally, we show that Krox-20, an important regulatory target of Oct-6 in Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent mechanism in these mice.
Ghazvini
Merhnaz
M
Department of Cell Biology and Genetics, Erasmus University Rotterdam, PO Box 1738, 3000DR Rotterdam, The Netherlands.
Mandemakers
Wim
W
Jaegle
Martine
M
Piirsoo
Marko
M
Driegen
Siska
S
Koutsourakis
Manousos
M
Smit
Xsander
X
Grosveld
Frank
F
Meijer
Dies
D
D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D002678:Chimera; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism; D051767:Early Growth Response Protein 2; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D050816:Octamer Transcription Factor-6; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000033:anatomy & histology / Q000254:growth & development*; D012583:Schwann Cells / Q000502:physiology*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D009419:Nerve Tissue Proteins; C494180:Pou3f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6