COLUMBIA UNIVERSITY • DEPARTMENT OF
Physiology and Cellular Biophysics

jd18@cumc.columbia.edu

CURRENT RESEARCH

We are studying the molecular and cellular events that regulate the early development and organization of the central nervous system. We focus on aspects of the guidance of axons as they form circuits. To determine the nature of axonal guidance cues and the mechanisms by which growth cones respond to them, we study the earliest axonal pathways in the developing spinal cord. This system allows us to ask questions of general relevance to the development of the CNS such as why and how do projection neurons extend axons across the midline? How are the various responses to distinct but simultaneous cues coordinated in the growth cone? We use a combination of in vitro assays in combination with antibodies and molecular markers that define cellular components of the developing spinal cord in genetically tractable models of mouse.

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We have identified several components of a guidance system that contributes to the projection patterns of subsets of spinal sensory relay neurons. Most projection neurons of the dorsal spinal cord share an initial axonal path: they extend axons circumferentially and ventrally away from the dorsal midline of the neural tube. But a decision is then made to form or join ipsilateral tracts or to cross the ventral midline and join contralateral tracts towards central targets. One aspect of our work is to examine how this choice is programmed in individual neurons and we are using neuron specific viral tracing techniques to define the developing central pathways.

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At a mechanistic level, we are interested in the cell biology underlying the orientation of the cytoskeleton of the growing tips of axons by guidance cues. We have found that bone morphogenetic factors (BMPs) act as guidance cues. BMPs have dual signaling roles, as both growth factors, activating transcriptional programs, and acute orienting factors, signaling the cytoskeleton in non-transcriptional ways. We are currently exploring the detailed mechanisms of BMP receptor activation that underlie these dual roles in dorsal spinal neurons.