Departments And Divisions
- Department of Physiology & Cellular Biophysics
- Department of Neuroscience
- Professor of Physiology & Cellular Biophysics
- Professor of Neuroscience
- Vice Chairman, Physiology & Cellular Biophysics
We are studying the molecular and cellular events that regulate the early development and organization of the central nervous system. After neuronal differentiation, axons extend towards their target cells within the central nervous system, navigating under the guidance of cues in the environment. To determine the nature of such cues and the mechanisms by which growth cones respond to them, we have analyzed the earliest axonal pathways in the developing spinal cord. Using in vitro assays in combination with antibodies and molecular markers that define cellular components of the developing spinal cord, we have identified several components of a guidance system that may contribute to the projection pattern of a subset of sensory relay neurons, the commissural neurons. Commissural neurons project circumferentially and ventrally away from the dorsal midline of the neural tube and towards and across the ventral midline of the spinal cord before turning to project towards higher spinal segments and supraspinal sites. Two groups of cells, located at the dorsal and ventral midlines and known as the roof plate and the floor plate, respectively, appear to act as sources of cues for commissural axons. The roof plate appears to direct initial axon extension away from the dorsal midline through the release of a diffusible chemorepellent, whereas the floor plate provides both contact-mediated and diffusible cues for commissural axon navigation towards and across the midline. We are currently trying to determine how roof plate- and floor plate-derived signals act to influence the direction of growth of commissural axons.
The ventral midline of the neural tube consists of several subgroups of cells that differ, according to their position in the rostro-caudal axis, in the expression of cellular markers and signaling molecules. Throughout the axis, these cells appear to have multiple roles in the patterning of adjacent cell types and axons. To begin to study the mechanisms underlying cell identity within the neural tube we have therefore examined the development of the ventral midline cell groups. By analyzing changes in neural cell identity and pattern within neural tube explants, we have shown that axial mesodermal cells of the notochord and prechordal mesoderm provide inductive signals that initiate the differentiation of the ventral midline and patterning of neurons within the neural plate. Sonic hedgehog appears to mediate the induction of floor plate by notochord, but in rostral regions sonic hedgehog appears to act cooperatively with another signaling molecule to generate ventral midline cells with rostral properties. Current experiments are directed at the molecular identification of mesoderm-derived inducing signals at different rostro-caudal levels and the characterization of the response of neuroepithelial cells to such signals.
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Honors & Awards
- 1976-1979 MRC Research Fellow
- 1979-1981 Harkness Fellow of the Commonwealth Foundation
- 1981-1983 Sloan Research Fellow of the Alfred P. Sloan Foundation
- 1985-1988 McKnight Foundation Scholar
- 1986-1990 Irma T Hirschl Career Scientist
- 1988-1991 The Esther and Joseph P Klingenstein Fund Fellow
- 1994-1997 McKnight Endowment Fund for Neuroscience Development Award
- Synapses and Circuits
- Cell Specification and Differentiation
- Axon Pathfinding and Synaptogenesis
- Cellular/Molecular/Developmental Neuroscience
Perron, J. C. and Dodd, J. (2012) Structural distinctions in BMPs underlie divergent signaling in spinal neurons. Neural Dev. Neural Development, 7:16.
Perron, J. C. and Dodd, J. (2011) Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways. Neural Dev. 6:36.
Perron, J. C. and Dodd, J. (2009) ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis. PLoS One. 4(12):e8198.
Wilson, S. I., Shafer, B., Lee, K. J. and Dodd, J. (2008) A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors. Neuron 59:413-424.
Dodd, J., and Kolodkin, A.L. (2005). Development: edging towards circuitry, behavior and disease. Curr Opin Neurobiol. 15:1-6. Review.
Butler ,S.J., and Dodd J. (2003). A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron. 38:389-401.
Augsburger, A., Schuchardt, A., Hoskins, S., Dodd, J., and Butler, S. (1999). BMPs as mediators of roof plate repulsion of commissural neurons. Neuron. 24:127-41.
Dale, K., Vesque, C., Sattar, N., Lints, T., Sampath, K., Furley, A., Dodd, J., Placzek, M. (1997). Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90:257-269.
Shah, S.B., Skromne, I., Hume, C.R., Kessler, D.S., Lee, K.J, Stern, C.D., and Dodd, J. (1997). Misexpression of chick Vg1 in the marginal zone induces primitive streak formation. Development 124:5127-5138.
Placzek, M., Jessell, T.M., Dodd, J. (1993). Induction of floor plate differentiation by contact-dependent, homeogenetic signals. Development 117:205-218.
Dodd, J., Jessell, T.M. (1988). Axon guidance and the patterning of neuronal connections. Science 242:692-699.