The research in my laboratory is aimed at identifying mechanisms that establish stereotyped patterns of connectivity in the developing vertebrate and invertebrate central nervous system (CNS). Our vertebrate studies are aimed at understanding how growing axons navigate through intermediate targets/choice points and ultimately connect with their appropriate targets, and how those axons, which leave the CNS, choose the appropriate exit point. The invertebrate studies are directed toward identifying molecular mechanisms that control dendrite branching. To achieve these goals, we work with both well-studied and understudied classes of vertebrate spinal interneurons and motor neurons and a unique C. elegans neuron that extends highly branched dendrites. Our main focus is on understanding the mechanisms that control the pathfinding of spinal commissural axons, a major class of midline-crossing axons in the developing CNS. In these studies, we use novel in vitro assay systems, chick in ovo electroporation and a large array of transgenic reporter, as well as, mutant mice to identify guidance cues and their corresponding receptors, which regulate the pathfinding of genetically distinct populations of spinal commissural axons. By manipulating guidance receptor expression in mouse and chick embryos, we are also investigating how dynamic changes in the spatial distribution of these receptors influence various aspects of commissural axon pathfinding within the spinal cord. In addition, we are identifying synaptic targets for genetically distinct commissural axons and elucidating the molecular mechanisms that guide specific subsets of commissural axons from the spinal cord to the brain. A parallel effort is aimed at identifying the molecular logic that regulates the development of spinal accessory motor neurons, a unique class of spinal motor neurons that projects axons to and through discrete and readily identifiable lateral exit points. These studies make use of cell surface markers and reporter mice that selectively label spinal accessory motor neurons and their axons, as well as our previous observation that a particular transcription factor is required for the exit of spinal accessory motor axons from the CNS. In ongoing studies, we are attempting to determine the mechanisms through which particular cell surface receptors facilitate the exit of these axons. In our C. elegans studies, we have carried large scale RNAi screens to identify molecules that regulate the branching of dendrites associated with the PVD neuron. Thus far, our results implicate a key role for dynein microtubule motors and associated proteins, as well as a protein that interacts with the Fragile-X Mental Retardation Protein, and basement membrane components, in regulating the proper formation of dendritic arbors in the C. elegans nervous system.
Bravo-Ambrosio, A, Mastick, G, Kaprielian, Z. Motor axon exit from the mammalian spinal cord is controlled by the homeodomain protein, Nkx2.9, via Robo-Slit signaling. Development 2012, 139: 1435-1446. http://dev.biologists.org/content/139/8/1435.long
Sakai, N, Kaprielian, Z. Guidance of longitudinally projecting axons in the developing central nervous system. Front Mol Neurosci 2012,5:59. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343325/
Bravo-Ambrosio, A, Kaprielian, Z. Crossing the Border: Molecular Control of Motor Axon Exit. Int J Mol Sci2011,12: 8539-8561. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257087/
Aguirre-Chen, C, Bulow, HE, Kaprielian, Z. C. elegans Bicd-1, Homolog of the Drosophila Dynein Accessory Factor, Bicaudal D, Regulates the Branching of PVD Sensory Neuron Dendrites. Development 2011, 138: 507-518. http://dev.biologists.org/content/138/3/507.long
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