Deletion of Nf1 in neurons induces increased axon collateral branching after dorsal root injury.
Ras-mediated signaling pathways participate in multiple aspects of neural development and function. For example, Ras signaling lies downstream of neurotrophic factors and Trk family receptor tyrosine kinases to regulate neuronal survival and morphological differentiation, including axon extension and target innervation. Neurofibromin, the protein encoded by the tumor suppressor gene Nf1, is a negative regulator of Ras [Ras-GAP (GTPase-activating protein)], and we previously demonstrated that Nf1 null embryonic sensory and sympathetic neurons can survive and differentiate independent of neurotrophin support. In this report, we demonstrate that Nf1 loss in adult sensory neurons enhances their intrinsic capacity for neurite outgrowth and collateral branching in vitro and in vivo after dorsal root injury. In contrast to the permanent sensory deficits observed in control mice after dorsal rhizotomy, neuron-specific Nf1 mutant mice spontaneously recover proprioceptive function. This phenomenon appears to be mediated both by a cell-autonomous capacity of spared Nf1-/- DRG neurons for increased axonal sprouting, and by non-cell-autonomous contribution from Nf1-/- neurons in the denervated spinal cord.
Romero
Mario I
MI
Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
Lin
Lu
L
Lush
Mark E
ME
Lei
Lei
L
Parada
Luis F
LF
Zhu
Yuan
Y
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D005727:Ganglia, Spinal / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D017353:Gene Deletion; D020868:Gene Silencing; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites; D025542:Neurofibromin 1 / Q000172:deficiency / Q000235:genetics*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D011434:Proprioception; D020127:Recovery of Function; D019051:Rhizotomy; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
D025542:Neurofibromin 1; C045073:Cre recombinase; D019426:Integrases