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Department of Biological Sciences
Office : Mackenzie Chown F223
Lab: Mackenzie Chown C203
Phone 905-688-5550 x3827
BA 1970 (Honors Biology) Amherst College (Amherst, Mass.)
MSc 1975, PhD 1978 (Zoology) University of New Hampshire, (Durham, NH)
CURRENT COURSES OFFERED
BIOL 3P28 Developmental Biology
BIOL 3P92 Advanced Developmental Biology
BIOL 4P28 Developmental Neurobiology
BIOL 5P28 Advanced Developmental Neurobiology
BIOL 5P87 Current Topics in Neurobiology
We study the role of retinoids such as all-trans (atRA) and 9-cis retinoic acids in neuronal growth, development and regeneration in both vertebrate and invertebrate model systems. We use the spinal cord of the adult newt (Notophthalmus viridescens) to examine the role of atRA in a system capable of epimorphic regeneration into adulthood.
We have found that atRA can promote neurite outgrowth and direct growth cone turning in cultured newt spinal cord explants and that this small molecule works through the specific nuclear receptor, retinoic acid receptor beta 2 (RARβ2). We have cloned the newt homolog of RARβ2 and have determined that, unlike in adult mammalian spinal cord tissue, expression of the newt receptor is maintained in normal spinal cord in the adult and upregulated after spinal cord injury. We are presently involved in studies to determine the precise function of atRA signaling in this process and to identify putative downstream targets of this pathway required for regeneration of the cord.
In collaboration with Gaynor Spencer in our department, we have extended our studies on the role of these retinoids in promoting and guiding outgrowth of isolated, identifiable neurons from the brain of the pond snail (Lymnaea stagnalis). We have provided evidence that both atRA and 9-cis RA can promote survival and outgrowth as well as provide directional cues in vitro for visceral F neurons and Pedal A ciliary motorneurons. Most recently we have provided strong evidence that these retinoids are acting via a novel non-genomic mechanism to elicit growth cone turning in these neurons , since turning in response to an applied gradient of atRA can still occur in isolated growth cones surgically removed from their cell bodies and nuclei. Studies are underway to decipher the precise mechanisms underlying this non-genomic form of retinoid signaling.
RECENT REPRESENTATIVE PUBLICATIONS
Carter, C. J., Farrar, N., Carlone, R. L. and and Spencer, G. E. (2010) A novel, non-genomic role for the retinoid X receptor (RXR) in growth cone turning of cultured molluscan neurons (Submitted, accepted with revision) Dev. Biol.
Farrar, N. R., Dmetrichuk, J. M., Carlone, R. L. and Spencer, G. E. (2009) A novel, non-genomic mechanism underlies retinoic-acid-induced growth cone turning. J. Neurosci. 29(45) 14136-14142
Dmetrichuk, J. M., Carlone, R. L., Jones, T. R. B., Vesprini, N. D. and G. E. Spencer (2008) Detection of endogenous retinoids in the molluscan CNS and characterization of the tropic and trophic actions of 9-cis retinoic acid on isolated neurons. J. Neurosci. 28:13014-13024.
Dmetrichuk, J. , Carlone, R. and Spencer, G. 2006 Retinoic acid induces neurite outgrowth and growth cone turning in invertebrate neurons. Dev. Biol. 294:39-49.
Dmetrichuk, J.M., G. E. Spencer and R. L. Carlone. (2005) Retinoic acid-dependent attraction of adult spinal cord axons towards regenerating newt limb blastemas in vitro. Dev. Biol. 281:112-120
Prince, D. and R. L. Carlone. (2003) Retinoic acid involvement in the reciprocal neurotrophic interactions between spinal cord and limb blastemas in vitro. Dev. Brain Res. 140:67-73.