Mammalian Motoneuron Axon Targeting Requires Receptor Protein Tyrosine Phosphatases σ and δ

By N. Uetani, Mélanie J. Chagnon, T. Kennedy, Y. Iwakura, M. Tremblay. Journal of Neuroscience, 2006

117 citations recorded by the source corpus.

The leukocyte common antigen-related (LAR) subfamily of receptor protein tyrosine phosphatases (RPTPs), LAR, RPTP-σ, and RPTP-δ, 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-σ and RPTP-δ are highly expressed in the developing mammalian nervous system, suggesting they might be functionally redundant. To test this hypothesis, we generated RPTP-σ and RPTP-δ (RPTP-σ/δ) double-mutant mice. Although embryonic day 18.5 RPTP-σ and RPTP-δ single-mutant embryos were viable, RPTP-σ/δ double mutants were paralyzed, were never observed to draw a breath, and died shortly after cesarean section. RPTP-σ/δ 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-σ/δ 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-σ and RPTP-δ complement each other functionally during mammalian development, and reveal an essential contribution of RPTP-σ and RPTP-δ to appropriate motoneuron axon targeting during mammalian axonogenesis.

Subfields: Cellular and Molecular Neuroscience, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/af4465ac7ddeab02ed306b27382fc3a0e2ed233e