Protein tyrosine phosphatase receptor type O inhibits trigeminal axon growth and branching by repressing TrkB and ret signaling

Graziana Gatto, Irina Dudanova, Philipp Suetterlin, Alun M. Davies, Uwe Drescher, John L. Bixby, Rüdiger Klein

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Axonal branches of the trigeminal ganglion (TG) display characteristic growth and arborization patterns during development. Subsets of TG neurons express different receptors for growth factors, but these are unlikely to explain the unique patterns of axonal arborizations. Intrinsic modulators may restrict or enhance cellular responses to specific ligands and thereby contribute to the development of axon growth patterns. Protein tyrosine phosphatase receptor type O (PTPRO), which is required for Eph receptor-dependent retinotectal development in chick and for development of subsets of trunk sensory neurons in mouse, may be such an intrinsic modulator of TG neuron development. PTPRO is expressed mainly in TrkB-expressing (TrkB+) and Ret+ mechanoreceptors within the TG during embryogenesis. In PTPRO mutant mice, subsets ofTGneurons grow longer and more elaborate axonal branches. Cultured PTPRO-/-TG neurons display enhanced axonal outgrowth and branching in response to BDNF and GDNF compared with control neurons, indicating that PTPRO negatively controls the activity of BDNF/TrkB and GDNF/Ret signaling. Mouse PTPRO fails to regulate Eph signaling in retinocollicular development and in hindlimb motor axon guidance, suggesting that chick and mouse PTPRO have different substrate specificities. PTPRO has evolved to fine tune growth factor signaling in a cell-type-specific manner and to thereby increase the diversity of signaling output of a limited number of receptor tyrosine kinases to control the branch morphology of developing sensory neurons. The regulation of Eph receptor-mediated developmental processes by protein tyrosine phosphatases has diverged between chick and mouse.

Original languageEnglish (US)
Pages (from-to)5399-5410
Number of pages12
JournalAnnals of internal medicine
Volume158
Issue number6
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Internal Medicine

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