title: Mammalian motoneuron axon targeting requires receptor protein tyrosine phosphatases sigma and delta.
abstract: The leukocyte common antigen-related (LAR) subfamily of receptor protein tyrosine phosphatases (RPTPs), LAR, RPTP-sigma, and RPTP-delta, regulate neuroendocrine development, axonal regeneration, and hippocampal long-term potentiation in mammals. In Drosophila, RPTPs are required for appropriate axon targeting during embryonic development. In contrast, deletion of any one of the three LAR-RPTP family members in mammals does not result in gross axon targeting defects. Both RPTP-sigma and RPTP-delta are highly expressed in the developing mammalian nervous system, suggesting they might be functionally redundant. To test this hypothesis, we generated RPTP-sigma and RPTP-delta (RPTP-sigma/delta) double-mutant mice. Although embryonic day 18.5 RPTP-sigma and RPTP-delta single-mutant embryos were viable, RPTP-sigma/delta double mutants were paralyzed, were never observed to draw a breath, and died shortly after cesarean section. RPTP-sigma/delta double mutants exhibit severe muscle dysgenesis and severe loss of motoneurons in the spinal cord. Detailed analysis of the projections of phrenic nerves in RPTP-sigma/delta double mutants indicated that these motoneuron axons emerge normally from the cervical spinal cord, but stall on reaching the diaphragm. Our results demonstrate that RPTP-sigma and RPTP-delta complement each other functionally during mammalian development, and reveal an essential contribution of RPTP-sigma and RPTP-delta to appropriate motoneuron axon targeting during mammalian axonogenesis.
authors.affiliation: McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Noriko
authors.initials: N
authors.lastname: Uetani
authors.forename: Mélanie J
authors.initials: MJ
authors.lastname: Chagnon
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000201:enzymology / Q000502:physiology*; D003643:Death; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005552:Forelimb / Q000196:embryology; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology; D009046:Motor Neurons / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D013116:Spinal Cord / Q000196:embryology / Q000201:enzymology
chemical_list: D017027:Protein Tyrosine Phosphatases; C490395:Ptprd protein, mouse; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2