Journal article

PI3-kinase delta enhances axonalPIP(3)to support axon regeneration in the adultCNS

Bart Nieuwenhuis, Amanda C Barber, Rachel S Evans, Craig S Pearson, Joachim Fuchs, Amy R MacQueen, Susan van Erp, Barbara Haenzi, Lianne A Hulshof, Andrew Osborne, Raquel Conceicao, Tasneem Z Khatib, Sarita S Deshpande, Joshua Cave, Charles Ffrench-Constant, Patrice D Smith, Klaus Okkenhaug, Britta J Eickholt, Keith R Martin, James W Fawcett Show all



Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol (3,4,5)-trisphosphate (PIP3 ). We demonstrate that adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However, in the CNS, axonal PIP3 decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect; however, expression of p110δ resto..

View full abstract


Awarded by MRC-Sackler, International Spinal Research Trust

Awarded by Wellcome Trust

Awarded by Czech Ministry of Education

Awarded by Medical Research Council MRC

Awarded by DFG

Awarded by EMBO ALTF

Awarded by BBSRC

Awarded by Biotechnology and Biological Sciences Research Council

Funding Acknowledgements

We acknowledge the Babraham Gene Targeting Facilities for the generation of the Rosa26 p110 mouse strains and would like to thank Dr. Len Stephens and Dr. Phill Hawkins (Babraham) for the gift of the GFP-AKT-PH mouse strain, and for their advice and support. RE, JWF, KRM, ACB, BN, RSE and CSP were supported by grants from MRC-Sackler, International Spinal Research Trust (NRB110), Wellcome Trust, ERA-NET NEURON grant AxonRepair, the European Union, the Operational Programme Research, Development and Education in the framework of the project "Centre of Reconstructive Neuroscience", Czech Ministry of Education, CZ.02.1.01/0.0./0.0/15_003/0000419, Medical Research Council MRC (MR/R004544/1, MR/R004463/1), Christopher and Dana Reeve Foundation, Cambridge Eye Trust, Fight for Sight, and National Eye Research Council and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. BJE funding was provided by the DFG (SFB 958, TP16; SFB TRR 186, TP10). SvE was funded by EMBO ALTF 1436-2015, and SvE and Cff-C by MS Society UK. KO laboratory funding was provided by the BBSRC (BBS/E/B/000C0409, BBS/E/B/000C0427) and the Wellcome Trust (095691/Z/11/Z).