Sensory and Developmental Neurobiology
We investigate sensory organs and particularly the uniquely specialized cells that detect external signals (the sensory receptor cells) and communicate this information to the brain (the primary sensory neurons). Our approach is to identify and characterize novel genes involved in the formation (during development or regeneration), function (as sensory transducers), dysfunction and death (causing diseases like deafness or neuropathic pain) of these cells. The genes we have studied so far encode ion channels (of the Deg/ENaC and TRP families) and transcriptional regulators (zinc-finger proteins, these studied in collaboration with Anne Duggan). We are interested in all forms of sensation but, as of now, have primarily explored the somatic (touch and pain), auditory and nasal sensory organs.
Sensory Neuron Development: We found Insm1, a zinc-finger gene regulator that determines the number of olfactory receptor neurons. Insm1 is expressed in the olfactory epithelium, as everywhere else in the developing nervous system, in late (but not early) progenitors and nascent (but not mature) neurons, and it functions by promoting the transition of neuroepithelial progenitors from apical, proliferative and uncommitted (i.e., neural stem cells) to basal, terminally-dividing and neuron-producing (1, 2). We are currently determining the role of Insm1 in other sensory organs, as well as elucidating the role of other novel neurodevelopmental genes.
Sensory Transduction: We pioneered a molecular model of how certain neurons can detect touch using DEG/ENaC channels and structural components of the extracellular matrix and the cytoskeleton (3, 4), characterized a major pain transduction channel (TRPA1; 5), and continue searching for sensory transducers, particularly ion channels.
Left: Pain-sensing TRPA1 channels in small (nociceptive) neurons of mouse dorsal root ganglia.
Middle/Right: Macromolecular Model of Touch Mechanotransduction in C. elegans.
Sensory Transduction: We pioneered a molecular model of how certain neurons can detect touch using DEG/ENaC channels and structural components of the extracellular matrix and the cytoskeleton (3, 4), characterized a major pain transduction channel (TRPA1; 5), and continue searching for sensory transducers, particularly ion channels.
We investigate sensory organs and particularly the uniquely specialized cells that detect external signals (the sensory receptor cells) and communicate this information to the brain (the primary sensory neurons). Our approach is to identify and characterize novel genes involved in the formation (during development or regeneration), function (as sensory transducers), dysfunction and death (causing diseases like deafness or neuropathic pain) of these cells. The genes we have studied so far encode ion channels (of the Deg/ENaC and TRP families) and transcriptional regulators (zinc-finger proteins, these studied in collaboration with Anne Duggan). We are interested in all forms of sensation but, as of now, have primarily explored the somatic (touch and pain), auditory and nasal sensory organs.
Sensory Neuron Development: We found Insm1, a zinc-finger gene regulator that determines the number of olfactory receptor neurons. Insm1 is expressed in the olfactory epithelium, as everywhere else in the developing nervous system, in late (but not early) progenitors and nascent (but not mature) neurons, and it functions by promoting the transition of neuroepithelial progenitors from apical, proliferative and uncommitted (i.e., neural stem cells) to basal, terminally-dividing and neuron-producing (1, 2). We are currently determining the role of Insm1 in other sensory organs, as well as elucidating the role of other novel neurodevelopmental genes.
Sensory Transduction: We pioneered a molecular model of how certain neurons can detect touch using DEG/ENaC channels and structural components of the extracellular matrix and the cytoskeleton (3, 4), characterized a major pain transduction channel (TRPA1; 5), and continue searching for sensory transducers, particularly ion channels.
Left: Pain-sensing TRPA1 channels in small (nociceptive) neurons of mouse dorsal root ganglia.
Middle/Right: Macromolecular Model of Touch Mechanotransduction in C. elegans.
Sensory Transduction: We pioneered a molecular model of how certain neurons can detect touch using DEG/ENaC channels and structural components of the extracellular matrix and the cytoskeleton (3, 4), characterized a major pain transduction channel (TRPA1; 5), and continue searching for sensory transducers, particularly ion channels.