title: Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway.
abstract: Fast nerve conduction relies on successive myelin segments that electrically isolate axons. Segment geometry-diameter and length-is critical for the optimization of nerve conduction and the molecular mechanisms allowing this optimized geometry are partially known. We show here that peripheral myelin elongation is dynamically regulated by stimulation of YAP (Yes-associated protein) transcription cofactor activity during axonal elongation and limited by inhibition of YAP activity via the Hippo pathway. YAP promotes myelin and non-myelin genes transcription while the polarity protein Crb3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP activity, therefore allowing for optimal myelin growth. Dystrophic Dy(2j/2j) mice mimicking human peripheral neuropathy with reduced internodal lengths have decreased nuclear YAP which, when corrected, leads to longer internodes. These data show a novel mechanism controlling myelin growth and nerve conduction, and provide a molecular ground for disease with short myelin segments.
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Ruani N
authors.initials: RN
authors.lastname: Fernando
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cotter
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Perrin-Tricaud
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Berthelot
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bartolami
authors.affiliation: ETH, Institute of Molecular Health Sciences, HPL F 36 Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: ETH, Institute of Molecular Health Sciences, HPL F 36 Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.affiliation: Institut des Neurosciences de Montpellier, INSERM U1051, University of Montpellier, Hopital Saint Eloi, 80 rue A. Fliche, 34090 Montpellier, France.
authors.forename: Nicolas
authors.identifier: http://orcid.org/0000-0002-1620-4046
authors.initials: N
authors.lastname: Tricaud
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C530695:Crb3 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases