SHP-2 mediates target-regulated axonal termination and NGF-dependent neurite growth in sympathetic neurons

Bo Chen, Latanya Hammonds-Odie, Jeanette Perron, Brian A. Masters, John Bixby

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The tyrosine phosphatase SHP-2 has been implicated in a variety of signaling pathways, including those mediated by neurotrophins in neurons. To examine the role of SHP-2 in the development of sympathetic neurons, we inhibited the function of SHP-2 in transgenic mice by overexpressing a catalytically inactive SHP-2 mutant under the control of the human dopamine β-hydroxylase promoter. Expression of mutant SHP-2 did not influence the survival, axon initiation, or pathfinding abilities of the sympathetic neurons. However, mutant SHP-2 expression resulted in an overproduction of sympathetic fibers in sympathetic target organs. This was due to interference with SHP-2 function, as overexpression of wild type SHP-2 had no such effect. In vitro, NGF-dependent neurite growth was inhibited in neurons expressing mutant SHP-2 but not in those expressing wild type SHP-2. Mutant (but not wt) SHP-2 expression also inhibited NGF-stimulated ERK activation. The NGF-dependent survival pathway was less affected than the neurite growth pathway. Our results suggest that NGF-regulated axon growth signals, and to a lesser degree survival signals, are mediated through a SHP-2-dependent pathway in sympathetic neurons. The increased sympathetic innervation in target tissues of neurons expressing mutant SHP-2 may result from interference with normal "stop" signals dependent on signaling by gradients of NGF.

Original languageEnglish
Pages (from-to)170-187
Number of pages18
JournalDevelopmental Biology
Volume252
Issue number2
DOIs
StatePublished - Dec 1 2002

Fingerprint

Nerve Growth Factor
Neurites
Neurons
Growth
Survival
Axons
Adrenergic Fibers
Nerve Growth Factors
Mixed Function Oxygenases
Phosphoric Monoester Hydrolases
Transgenic Mice
Tyrosine
Dopamine

Keywords

  • ERKs
  • Neurotrophins
  • Transgenic mouse
  • Tyrosine phosphatases

ASJC Scopus subject areas

  • Developmental Biology

Cite this

SHP-2 mediates target-regulated axonal termination and NGF-dependent neurite growth in sympathetic neurons. / Chen, Bo; Hammonds-Odie, Latanya; Perron, Jeanette; Masters, Brian A.; Bixby, John.

In: Developmental Biology, Vol. 252, No. 2, 01.12.2002, p. 170-187.

Research output: Contribution to journalArticle

Chen, Bo ; Hammonds-Odie, Latanya ; Perron, Jeanette ; Masters, Brian A. ; Bixby, John. / SHP-2 mediates target-regulated axonal termination and NGF-dependent neurite growth in sympathetic neurons. In: Developmental Biology. 2002 ; Vol. 252, No. 2. pp. 170-187.
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