Sonic hedgehog signalling in neurons of adult ventrolateral nucleus tractus solitarius.
The transmembrane receptor Patched (Ptc) mediates the action of the diffusing factor Sonic hedgehog (Shh), which is implicated in establishing morphogenetic gradients during embryonic development. Whereas alteration of Ptc function is associated with developmental abnormalities and brain tumors, its functional activity and roles in the adult brain have yet to be elucidated. Here we describe the complementary pattern of Shh and Ptc expression in the rat dorsal vagal motor nucleus and the ventrolateral nucleus tractus solitarius (vNTS), respectively. Those two interconnected structures regulate the cardiorespiratory function during hypoxia. Bath application of a subnanomolar concentration of aminoterminal Shh protein (ShhN) to a slice preparation of the vNTS induces a rapid decrease in neuronal firing followed by a bursting activity that propagates in the neuronal network. Intracellular current injections show that bursts result from an action on the neuronal membrane electro-responsiveness. Both inhibiting and bursting effects are blocked by the monoclonal Shh antibody 5E1 and may require the Ptc binding site of ShhN. Thus, ShhN acting on specific neuronal sites controls electrophysiological properties of differentiated neurons of the vNTS. We speculate on a retrocontrol of cardiorespiratory signals in the vNTS, by Shh generated in dorsal vagal motoneurons.
Pascual
Olivier
O
Neurobiologie Génétique et Intégrative, UPR 2216-CNRS, Institute de Neurobiologie Alfred Fessard, IFR 2118-CNRS, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Traiffort
Elisabeth
E
Baker
Darren P
DP
Galdes
Alphonse
A
Ruat
Martial
M
Champagnat
Jean
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D053823:Hedgehog Proteins; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017552:Solitary Nucleus / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010446:Peptide Fragments; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D000469:Alkaline Phosphatase; C013411:biocytin; D008239:Lysine