CURRENT PROJECTS
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Title: Cellular Mechanisms Underlying Growth Cone Turning Induced by Diffusible Cues.
Principal Investigator: James Zheng, Ph.D.
Research Summary:
Formation of specific nerve connections during development requires the guidance of the growing tip of elongating axons, the growth cone, to its correct target cells. Growth cones respond to a variety of attractive or repulsive guidance molecules present in the environment that are either diffusible or surface-bound by turning towards or away, respectively. The cellular processes by which a growth cone detects different diffusible cues and alters its direction of extension remain to be elucidated. In this study, we aim to understand how a growth cone detects the extracellular gradients of different molecules, relays the directional information intracellularly, and makes appropriate changes in its direction of extension. Our working hypothesis is as follows: gradients of activation of cell-specific receptors for different diffusible cues, mediated by different second messengers and kinases, all lead to a cytoplasmic gradient in the activation of a common set of proteins in the growth cone. The activated proteins in turn regulate cytoskeletal dynamics at the growth cone asymmetrically to result in an asymmetric modulation of growth cone motility, leading to the turning response. Using neuronal cultures prepared from Xenopus embryos, we will test our hypothesis. Specifically we will determine: (1) the precise role of second messengers Ca2+ and cAMP in encoding the directional information to direct the growth cone extension; (2) the sequence of asymmetric cellular events associated with growth cone motility that are common and essential for turning of growth cones induced by different attractants and repellents; (3) the asymmetric cytoskeletal and membranous events associated with the turning of the growth cone. The scheme underlying these studies is the common mechanisms underlying the turning of growth cones induced by different diffusible molecules. Elucidation of cellular and molecular mechanisms involved in growth cone guidance is critical for our understanding of the development of nervous systems in normal and pathological conditions. Furthermore, the results from this study will provide important insights on the “missing link” between various extracellular cues and the regulated nerve growth.
Funding sources:
- Foundation of the University of Medicine and Dentistry of New Jersey (UMDNJ Foundation);
- American Heart Association;
- National Institute of Neural Disorder and Stroke (NINDS), NIH
Title: Ca2+ Signaling in Growth Cone Guidance
Principal Investigator: James Zheng, Ph.D.
Research Summary: Coming soon.
Funding source(s): National Science Foundation
Other ongoing projects:
- Cytoskeletal dynamics in growth cones;
- Development of neuronal polarity;
- Synaptogenesis and plasticity;
- Cell biology of neuronal migration.
Note: All research performed in the lab is strictly adhered to NIH guidelines. For more information, please contact James Zheng.