Professor Emeritus, Biological Sciences
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 most recently are involved in studies to determine the precise function of atRA signaling in this process and to identify putative upstream regulators and downstream targets of this pathway required for regeneration of the cord. We have identified two microRNAs, miR-133a and miR-21, involved in regulating RARβ2 synthesis in the ependymoglial cells of the caudal spinal 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. These include an examination of the role of miR-124 in the regulation of local (growth cone specific) protein synthesis as cells respond chemotactically to a gradient of retinoic acid.
Rand, C, Spencer G, Carlone, R. (2017). Retinoic acid as a chemoattractant for embryonic spinal cord neurons of the African clawed frog, Xenopus laevis. Submitted Canadian J. of Zoology.
Lepp, A C, Haj-Ahmad, L, Rozema, D, Wlodarek, L, Kubarakos, E, Carlone , R. (2017). Inhibition of retinoic acid signaling with DEAB inhibits tail regeneration and alters miR-21 expression and targeting of jagged in the ependymoglial cells of the newt caudal spinal cord. Submitted Developmental Dynamics
Lepp, A C and Carlone, R L. (2015). MicroRNA dysregulation in response to RARβ2 inhibition reveals a negative feedback loop between microRNAs 1, 133a and RARβ2 during tail and spinal cord regeneration in the adult newt. Developmental Dynamics. 244: 1519-1537
Carter, CJ, Rand, C, Mohammad, I, Lepp, A, Vesprini, N, Wiebe, O, Carlone, R and Spencer, G. (2015). Expression of a retinoic acid receptor(RAR)-like protein in the embryonic and adult nervous system of a protostome species. Journal of Experimental Zoology (Mol. Dev. Evol.). 324B: 51-67.
Lepp, A and Carlone, R. (2014). RARβ2 expression is induced by the down-regulation of micro RNA 133a during caudal spinal cord regeneration in the adult newt. Developmental Dynamics. 243(12): 1581-1590.
Tattersall GJ, Tyson TM, Lenchyshyn, JR, Carlone RL. (2012). Temperature preference during forelimb regeneration in the red-spotted newt, Notophthalmus viridescens. Journal of Experimental Zoology. 317:248-258.
Szuroczki D, Vesprini ND, Jones TRB, Spencer GE, Carlone RL. (2011). Presence of Ribeiroia ondatrae in the developing anuran limb disrupts retinoic acid levels. Parasitology Research. 110: 49-59.
Carter C, Clark A, Spencer GE, Carlone RL. (2011). Cloning and expression of a retinoic acid receptor β2 subtype from the adult newt: Evidence for an early role in tail and caudal spinal cord regeneration. Developmental Dynamics. 240: 2613-2625.
BIOL 3P28 Developmental Biology
BIOL 3P92 Advanced Developmental Biology
BIOL 4P28 Developmental Neurobiology
BIOL 5P28 Advanced Developmental Neurobiology
BIOL 5P87 Current Topics in Neurobiology
BA 1970 (Honors Biology) Amherst College (Amherst, Mass.)
MSc 1975, PhD 1978 (Zoology) University of New Hampshire, (Durham, NH)