TY - JOUR
T1 - Protein tyrosine phosphatase receptor type O regulates development and function of the sensory nervous system
AU - Gonzalez-Brito, Manuel R.
AU - Bixby, John L.
N1 - Funding Information:
We thank Dr. Roger Wiggins for the generous donation of the PTPRO mouse mutants, and Beata Frydel and Dansha He for technical assistance with immunohistochemical preparation and stereotactic analysis. We are grateful for the technical assistance of Dr. Michael Nares and Walter Zegara, Cesar Garcia-Canet, Farid Alam, and Rochelle Marill for their help with mouse genotyping and scoring of the behavioral sensory exams. In addition, we acknowledge Dr. Dan Liebl, Dr. Pedro Beltran, and Eli Weaver for their expertise in mouse husbandry and genotyping. We appreciate the advice and guidance given by Drs. Vance Lemmon and Pantelis Tsoulfas during review of this manuscript. This work was supported by the Pediatric Critical Care Scientist Developmental Program , NICHD Grant Award K12-HD047349 to M.R.G.-B., and NIH grants R01NS059866 and R01-NS38920 to J.L.B .
PY - 2009/11
Y1 - 2009/11
N2 - The roles of protein tyrosine phosphatases (PTPs) in differentiation and axon targeting by dorsal root ganglion (DRG) neurons are essentially unknown. The type III transmembrane PTP, PTPRO, is expressed in DRG neurons, and is implicated in the guidance of motor and retinal axons. We examined the role of PTPRO in DRG development and function using PTPRO-/- mice. The number of peptidergic nociceptive neurons in the DRG of PTPRO-/- mice was significantly decreased, while the total number of sensory neurons appeared unchanged. In addition, spinal pathfinding by both peptidergic and proprioceptive neurons was abnormal in PTPRO-/- mice. Lastly, PTPRO-/- mice performed abnormally on tests of thermal pain and sensorimotor coordination, suggesting that both nociception and proprioception were perturbed. Our data indicate that PTPRO is required for peptidergic differentiation and process outgrowth of sensory neurons, as well as mature sensory function, and provide the first evidence that RPTPs regulate DRG development.
AB - The roles of protein tyrosine phosphatases (PTPs) in differentiation and axon targeting by dorsal root ganglion (DRG) neurons are essentially unknown. The type III transmembrane PTP, PTPRO, is expressed in DRG neurons, and is implicated in the guidance of motor and retinal axons. We examined the role of PTPRO in DRG development and function using PTPRO-/- mice. The number of peptidergic nociceptive neurons in the DRG of PTPRO-/- mice was significantly decreased, while the total number of sensory neurons appeared unchanged. In addition, spinal pathfinding by both peptidergic and proprioceptive neurons was abnormal in PTPRO-/- mice. Lastly, PTPRO-/- mice performed abnormally on tests of thermal pain and sensorimotor coordination, suggesting that both nociception and proprioception were perturbed. Our data indicate that PTPRO is required for peptidergic differentiation and process outgrowth of sensory neurons, as well as mature sensory function, and provide the first evidence that RPTPs regulate DRG development.
KW - Axon guidance
KW - Central afferent
KW - Nociception
KW - Pain
KW - Tyrosine phosphorylation
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U2 - 10.1016/j.mcn.2009.09.009
DO - 10.1016/j.mcn.2009.09.009
M3 - Article
C2 - 19800005
AN - SCOPUS:70350778444
VL - 42
SP - 458
EP - 465
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
SN - 1044-7431
IS - 4
ER -