Postnatal Schwann cell proliferation but not myelination is strictly and uniquely dependent on cyclin-dependent kinase 4 (cdk4)

Molecular and Cellular Neurosciences
Suzana AtanasoskiUeli Suter

Abstract

Peripheral myelin formation depends on axonal signals that tightly control proliferation and differentiation of the associated Schwann cells. Here we demonstrate that the molecular program controlling proliferation of Schwann cells switches at birth. We have analyzed the requirements for three members of the cyclin-dependent kinase (cdk) family in Schwann cells using cdk-deficient mice. Mice lacking cdk4 showed a drastic decrease in the proliferation rate of Schwann cells at postnatal days 2 and 5, but proliferation was unaffected at embryonic day 18. In contrast, ablation of cdk2 and cdk6 had no significant influence on postnatal Schwann cell proliferation. Taken together, these findings indicate that postnatal Schwann cell proliferation is uniquely controlled by cdk4. Despite the lack of the postnatal wave of Schwann cell proliferation, axons were normally myelinated in adult cdk4-deficient sciatic nerves. Following nerve injury, Schwann cells lacking cdk4 were unable to re-enter the cell cycle, while Schwann cells deficient in cdk2 or cdk6 displayed proliferation rates comparable to controls. We did not observe compensatory effects such as elevated cdk4 levels in uninjured or injured nerves of cdk2 or cdk6-deficient mice. Ou...Continue Reading

References

Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Aug 1, 2000·The Journal of Biological Chemistry·K L FergusonR S Slack
Dec 26, 2001·Molecular and Cellular Neurosciences·S AtanasoskiU Suter
Apr 6, 2002·Biological Chemistry·Christian S LobsigerUeli Suter
Jul 2, 2002·Journal of Anatomy·K R Jessen, R Mirsky
May 3, 2003·Molecular and Cellular Neurosciences·Dino P LeoneUeli Suter
Aug 19, 2003·Nature Genetics·Sagrario OrtegaMariano Barbacid
Oct 17, 2003·Current Biology : CB·Cyril BerthetPhilipp Kaldis
Jan 7, 2004·Cancer Cell·Ewa SicinskaPiotr Sicinski
Aug 18, 2004·Neuron·Suzana AtanasoskiUeli Suter
Sep 2, 2004·Cell·Michele Pagano, Peter K Jackson
Sep 2, 2005·Nature Reviews. Neuroscience·Kristjan R Jessen, Rhona Mirsky
Oct 21, 2005·Trends in Biochemical Sciences·Marcos Malumbres, Mariano Barbacid
Nov 18, 2005·Injury·Elizabeth O JohnsonPanayotis N Soucacos
Feb 17, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suzana AtanasoskiUeli Suter
May 9, 2006·Developmental Cell·Cyril BerthetPhilipp Kaldis
Jun 1, 2007·Molecular Oncology·Cédric BarrièreMariano Barbacid

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Citations

Apr 20, 2011·The Journal of Cell Biology·Céline CaillavaAnne Baron-Van Evercooren
Feb 15, 2011·Stem Cells·Pierre BeukelaersBrigitte Malgrange
Jan 22, 2014·Glia·Robin J M Franklin, Vittorio Gallo
Apr 26, 2017·International Journal of Molecular Medicine·Bin PanShi-Qing Feng
Apr 22, 2017·Oncotarget·Alejandra M PetrilliCristina Fernández-Valle
Jun 9, 2020·Molecular Neurobiology·Alice Grison, Suzana Atanasoski

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