TY - JOUR
T1 - Targeted expression of an oncogenic adaptor protein v-Crk potentiates axonal growth in dorsal root ganglia and motor neurons in vivo
AU - Weinstein, David E.
AU - Dobrenis, Kostantin
AU - Birge, Raymond B.
N1 - Funding Information:
This research was supported by NIH grant GM 55760 and a Muscular Dystrophy Grant to RBB. DW was supported by an International Spinal Research Trust (STR022) and a fund from the MS Society RS-2785A2. We would like to thank Tomoyuki Shishido and J. Eduardo Fajardo for critically reading the manuscript.
PY - 1999/8/5
Y1 - 1999/8/5
N2 - The ability of neurons to survive and to target axonal growth requires a coordinated series of cell extrinsic and intrinsic events. Previously, in a cellular model for neuronal differentiation, we showed that pheochromocytoma (PC12) cells expressing v-Crk, an oncogenic form of the SH2/SH3-containing c-Crk adaptor protein, potentiates axonal growth and prolongs nerve growth factor (NGF)-independent survival. In the present study, we have generated transgenic mice that express v-Crk in sensory, motor, and enteric neurons by placing v-crk under the control of the neuron-specific peripherin promoter. In contrast to wild-type (wt) mice, dorsal root ganglia (DRG) neurons explanted from post-natal day 1 transgenic mice demonstrated a reduced dependence on trophic factors for both survival and axonogenesis. v-Crk also caused an increase in the number of surviving spinal motor neurons (SMN), and interestingly, upon staining of sternomastoid muscle fibers with rhodamine conjugated α-bungarotoxin, many muscle fibers displayed an apparent increase in volume of motor end plates, and an increase in complexity of neuromuscular junctions (NMJ). Our data suggest that v-Crk may be involved in transducing extracellular signals to regulate cytoskeletal organization, and may act on an intrinsic determinant for axonal growth in a variety of neural types including sensory and motor neurons during development. Copyright (C) 1999 Elsevier Science B.V.
AB - The ability of neurons to survive and to target axonal growth requires a coordinated series of cell extrinsic and intrinsic events. Previously, in a cellular model for neuronal differentiation, we showed that pheochromocytoma (PC12) cells expressing v-Crk, an oncogenic form of the SH2/SH3-containing c-Crk adaptor protein, potentiates axonal growth and prolongs nerve growth factor (NGF)-independent survival. In the present study, we have generated transgenic mice that express v-Crk in sensory, motor, and enteric neurons by placing v-crk under the control of the neuron-specific peripherin promoter. In contrast to wild-type (wt) mice, dorsal root ganglia (DRG) neurons explanted from post-natal day 1 transgenic mice demonstrated a reduced dependence on trophic factors for both survival and axonogenesis. v-Crk also caused an increase in the number of surviving spinal motor neurons (SMN), and interestingly, upon staining of sternomastoid muscle fibers with rhodamine conjugated α-bungarotoxin, many muscle fibers displayed an apparent increase in volume of motor end plates, and an increase in complexity of neuromuscular junctions (NMJ). Our data suggest that v-Crk may be involved in transducing extracellular signals to regulate cytoskeletal organization, and may act on an intrinsic determinant for axonal growth in a variety of neural types including sensory and motor neurons during development. Copyright (C) 1999 Elsevier Science B.V.
KW - Actin cytoskeleton
KW - Dorsal root ganglion
KW - Neuromuscular junction
KW - Neurotrophin
KW - SH2/SH3 domain
KW - Transgenic mouse
KW - Tyrosine kinase
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U2 - 10.1016/S0165-3806(99)00072-3
DO - 10.1016/S0165-3806(99)00072-3
M3 - Article
C2 - 10446344
AN - SCOPUS:0032813430
SN - 0165-3806
VL - 116
SP - 29
EP - 39
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 1
ER -