Multiple Roles for Hepatocyte Growth Factor in Sympathetic Neuron Development

Maina, Flavio; Hilton, Mark; Andrés, Rosa; Wyatt, Sean; Klein, Rüdiger; Davies, Alun M.

doi:10.1016/s0896-6273(00)80466-3

Cited by 138 publications

(120 citation statements)

References 43 publications

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“…Both uPA and tPA have been shown to cleave and thereby activate the plasminogen-related growth factor, prohepatocyte growth factor/scatter factor (HGF/SF). HGF/SF is a significant growth-promoting and survival factor for sensory and motor neurons (Yamamoto et al, 1997;Maina et al, 1998;Yang et al, 1998). HGF has been shown to promote sympathetic neuron axonal growth and increase the forward rate of sympathetic neurite outgrowth in culture.…”

Section: Discussionmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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Peripheral nerve regeneration is dependent on the ability of regenerating neurites to migrate through cellular debris and altered extracellular matrix at the injury site, grow along the residual distal nerve sheath conduit, and reinnervate synaptic targets. In cell culture, growth cones of regenerating axons secrete proteases, specifically plasminogen activators (PAs), which are believed to facilitate growth cone movement by digesting extracellular matrices and cell adhesions. In this study, the PA system was shown to be specifically activated in sensory neurons after sciatic nerve crush in adult mice. The number of sensory neurons expressing urokinase PA receptor (uPAR) mRNA levels increased above sham levels by 8 hr after crush, whereas the number of sensory neurons expressing uPA and tissue PA (tPA) mRNAs was significantly increased by 3 d after crush. PA mRNA levels were also increased at the crush site, with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d. PA-dependent enzymatic activity was significantly increased from 1 to 7 d after crush in nerves that had been crushed compared with uncrushed nerves. Immunohistochemistry showed that tPA was localized within regenerating axons of the sciatic nerve. There were no significant changes in plasminogen activator inhibitor 1 activity between crush and sham after the injury. These results clearly demonstrated that after injury the PA system was rapidly induced in sensory neurons, where it may play an important role in nerve regeneration in vivo.

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Section: Discussionmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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“…Ablation of the Hgf or Met genes results in complete absence of this specific muscle type, leaving all other muscle groups unaffected 104,105,106 . Finally, disruption of HGF-MET function affects the proper wiring of the nervous system, leading to reduced survival of sensory and sympathetic neurons as well as impaired outgrowth and fasciculation (axon bundling) of certain motor nerves 110,111,112 .…”

Section: Met Signalling In Development and Diseasementioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,058

1,076

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The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

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“…For behavioral studies, we used adult (2-3 months old) male transgenic mice. The NesMet mutants were obtained through a genetic setting combining a conditional met allele [met fl (Huh et al, 2004)], a signaling-deficient met allele [met d (Maina et al, 1996(Maina et al, , 1998], and a strain in which Cre recombinase expression is driven by the nervous system-specific enhancer of nestin (Tronche et al, 1999). To generate the Met LacZ/ϩ mice, a loxP-flanked-neostop cassette has been inserted into exon 12 of the met locus, resulting in a loss of function of the met gene.…”

Section: Animals and Genotype Analysismentioning

confidence: 99%

Pool-Specific Regulation of Motor Neuron Survival by Neurotrophic Support

Lamballe

Genestine²,

Caruso³

et al. 2011

J. Neurosci.

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The precise control of motor neuron (MN) death and survival following initial innervation of skeletal muscle targets is a key step in sculpting a functional motor system, but how this is regulated at the level of individual motor pools remains unclear. Hepatocyte growth factor (HGF) and its receptor Met play key developmental roles in both muscle and MNs. We generated mice (termed "Nes-Met") in which met is inactivated from midembryonic stages onward in the CNS only. Adult animals showed motor behavioral defects suggestive of impaired innervation of pectoral muscles. Correspondingly, in neonatal spinal cords of Nes-Met mutants, we observed death of a discrete population of pea3-expressing MNs at brachial levels. Axonal tracing using pea3 reporter mice revealed a novel target muscle of pea3-expressing MNs: the pectoralis minor muscle. In Nes-Met mice, the pectoralis minor pool initially innervated its target muscle, but required HGF/Met for survival, hence for proper maintenance of muscle innervation. In contrast, HGF/Met was dispensable for the survival of neighboring Met-expressing MN pools, despite its earlier functions for their specification and axon growth. Our results demonstrate the exquisite degree to which outcomes of signaling by receptor tyrosine kinases are regulated on a cell-by-cell basis. They also provide a model for one way in which the multiplicity of neurotrophic factors may allow for regulation of MN numbers in a pool-specific manner.

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Multiple Roles for Hepatocyte Growth Factor in Sympathetic Neuron Development

Cited by 138 publications

References 43 publications

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

MET signalling: principles and functions in development, organ regeneration and cancer

Pool-Specific Regulation of Motor Neuron Survival by Neurotrophic Support

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