Targeted expression of an oncogenic adaptor protein v-Crk potentiates axonal growth in dorsal root ganglia and motor neurons in vivo

David E. Weinstein, Kostantin Dobrenis, Raymond B. Birge

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalDevelopmental Brain Research
Volume116
Issue number1
DOIs
StatePublished - Aug 5 1999

Fingerprint

Oncogene Protein v-crk
Spinal Ganglia
Motor Neurons
Neurons
Proto-Oncogene Proteins c-crk
Transgenic Mice
Growth
Peripherins
Motor Endplate
Bungarotoxins
Muscles
Rhodamines
Neuromuscular Junction
PC12 Cells
Pheochromocytoma
Nerve Growth Factor
Sensory Receptor Cells
Staining and Labeling

Keywords

  • Actin cytoskeleton
  • Dorsal root ganglion
  • Neuromuscular junction
  • Neurotrophin
  • SH2/SH3 domain
  • Transgenic mouse
  • Tyrosine kinase

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

Targeted expression of an oncogenic adaptor protein v-Crk potentiates axonal growth in dorsal root ganglia and motor neurons in vivo. / Weinstein, David E.; Dobrenis, Kostantin; Birge, Raymond B.

In: Developmental Brain Research, Vol. 116, No. 1, 05.08.1999, p. 29-39.

Research output: Contribution to journalArticle

@article{32da468dbae04eb2a1276cf9d74c553b,
title = "Targeted expression of an oncogenic adaptor protein v-Crk potentiates axonal growth in dorsal root ganglia and motor neurons in vivo",
abstract = "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.",
keywords = "Actin cytoskeleton, Dorsal root ganglion, Neuromuscular junction, Neurotrophin, SH2/SH3 domain, Transgenic mouse, Tyrosine kinase",
author = "Weinstein, {David E.} and Kostantin Dobrenis and Birge, {Raymond B.}",
year = "1999",
month = "8",
day = "5",
doi = "10.1016/S0165-3806(99)00072-3",
language = "English (US)",
volume = "116",
pages = "29--39",
journal = "Developmental Brain Research",
issn = "0165-3806",
publisher = "Elsevier BV",
number = "1",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=0032813430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032813430&partnerID=8YFLogxK

U2 - 10.1016/S0165-3806(99)00072-3

DO - 10.1016/S0165-3806(99)00072-3

M3 - Article

C2 - 10446344

AN - SCOPUS:0032813430

VL - 116

SP - 29

EP - 39

JO - Developmental Brain Research

JF - Developmental Brain Research

SN - 0165-3806

IS - 1

ER -