Somatosensory System Development and Pathology

Patrick CARROLL

 INM - U 1051

 80, rue Augustin Fliche, 34091 Montpellier

Phone: +33 4 99 63 60 41

Email: carroll@univ-montp2.fr

Website

The sensori-motor system regulates normal voluntary motor function, but also important spinal reflex systems that control posture, coordinated movements and protective reflexes. This system involves interactions between peripheral targets such as muscles, tendons, specialized sensory structures in the in skin, motoneurons and interneurons in the spinal cord and sensory neurons of the spinal ganglia. Many questions remain unanswered as to how this integrated system is established during development and altered in pathological conditions. Current research axes of our team:

i) Roles of phylogenetically conserved transcription factors in the development of sensorimotor circuit neurons. We identified transcription factors expressed in functionally-identified sub-types of somatosensory neurons and motoneurons in mice and flies that control their correct development. We are now trying to nail down the transcriptional programs controlled by these factors.

ii) Regeneration of periphery nerve after traumatic injury. We have developed novel methods to modify the neurite growth rates of injured sensory neurons. With the aim of better understanding and controlling peripheral regeneration, we are studying the molecular bases of these effects.

ii) Identification of inhibitors of a novel neuropathic pain mechanism. We identified a novel ligand/receptor system that plays a role in neuropathic pain. A project aimed at identifying chemical inhibitors of this pathway is underway.

Keywords: dorsal root ganglion; neuronal specification; mechanosensation; pain mechanisms; regeneration;

Main publications

• Ventéo S, Bourane S, Méchaly I, Sar S, Samad O, Puech S, Blostein R, Valmier J, Pattyn A and Carroll P (2011) Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons. PlosOne (in press)
• Grimal S, Puech S, Wagener R, Ventéo S, Carroll P, Fichard-Carroll A. (2010) Collagen XXVIII is a distinctive component of the peripheral nervous system nodes of Ranvier and surrounds nonmyelinating glial cells. Glia. 58:1977-87.
• Bourane S, Garces A, Venteo S, Pattyn A, Hubert T, Fichard A, Puech S, Boukhaddaoui H, Baudet C, Takahashi S, Valmier J and Carroll P. (2009). Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signalling. Neuron 64(6):857-70.
• Ohayon D, Pattyn A, Valmier J, Carroll P and Garces A (2009). The transcription factor zfh1 controls the survival of peripheral subperineurial glia by antagonizing a JNK-dependent apoptotic pathway. EMBO J. 28(20):3228-43.
• Hubert T, Bourane S, Ventéo S, Mechaly I, Puech S, Valmier J, Carroll P and Fichard-Carroll A (2007). Fibroblast growth factor homologous factor 1 (FHF1) is expressed in a sub-population of CGRP neurons in the murine Dorsal Root Ganglia. J Comp Neurol. Apr 1;507(4):1588-601.
• Bourane S, Mechaly I, Venteo S, Garces A, Fichard A, Valmier J and Carroll P (2007). A SAGE-based screen for genes expressed in sub-populations of neurons in the mouse dorsal root ganglion. BMC Neurosci. 8(1):97
• Mechaly I, Bourane S, Piquemal D, Al-Jumaily M, Venteo S, Puech S, Scamps F, Valmier J and Carroll P (2006) Gene profiling during development and after a peripheral nerve traumatism reveals genes specifically induced by injury in dorsal root ganglia. Mol. Cell. Neurosci. 32:217−29.
• Rossel M, Loulier K, Feuillet C, Alonso S and Carroll P (2005) Reelin signaling is necessary for a specific step in the migration of hindbrain efferent neurons. Development, 132;1175-1185.
• Dubreuil AS, Boukhaddaoui H, Desmadryl G, Martinez-Salgado C, Lewin G, Carroll P, Valmier J and Scamps F (2004). Role of T-type calcium current in identified D-hair mechanoreceptor neurons studied in vitro. J. Neurosci. 24:8480-8484
• Hack I., Bancila M., Loulier K., Carroll P. and Cremer H. (2002) "Reelin is a detachment signal in tangential chain migration during postnatal neurogenesis". Nature neuroscience 5 : 939-45