First Author | Uetani N | Year | 2006 |
Journal | J Neurosci | Volume | 26 |
Issue | 22 | Pages | 5872-80 |
PubMed ID | 16738228 | Mgi Jnum | J:109122 |
Mgi Id | MGI:3625794 | Doi | 10.1523/JNEUROSCI.0386-06.2006 |
Citation | Uetani N, et al. (2006) Mammalian motoneuron axon targeting requires receptor protein tyrosine phosphatases sigma and delta. J Neurosci 26(22):5872-80 |
abstractText | 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. |