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ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75(NTR)-dependent mechanism

Howard, Laura, Wyatt, Sean Lee ORCID:, Nagappan, Guhan and Davies, Alun M. ORCID: 2013. ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75(NTR)-dependent mechanism. Development 140 (10) , pp. 2108-2117. 10.1242/dev.085266

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The somatosensory and sympathetic innervation of the vertebrate head is derived principally from the neurons of trigeminal and superior cervical ganglia (SCG), respectively. During development, the survival of both populations of neurons and the terminal growth and branching of their axons in the tissues they innervate is regulated by the supply of nerve growth factor (NGF) produced by these tissues. NGF is derived by proteolytic cleavage of a large precursor protein, proNGF, which is recognised to possess distinctive biological functions. Here, we show that proNGF promotes profuse neurite growth and branching from cultured postnatal mouse SCG neurons. In marked contrast, proNGF does not promote the growth of trigeminal neurites. Studies using compartment cultures demonstrated that proNGF acts locally on SCG neurites to promote growth. The neurite growth-promoting effect of proNGF is not observed in SCG neurons cultured from p75NTR-deficient mice, and proNGF does not phosphorylate the NGF receptor tyrosine kinase TrkA. These findings suggest that proNGF selectively promotes the growth of neurites from a subset of NGF-responsive neurons by a p75NTR-dependent mechanism during postnatal development when the axons of these neurons are ramifying within their targets in vivo.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords: Proneurotrophins; p75(NTR); Neurite growth; Sympathetic neurons; Mouse
Publisher: The Company of Biologists
ISSN: 0950-1991
Date of First Compliant Deposit: 30 March 2016
Last Modified: 03 May 2023 17:10

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