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Spatial Signaling and Directional Control in Axon Guidance

by
Liang Han
M.S., 2004
Tsinghua University
Beijing, China

Thesis Advisor: James Q. Zheng
Graduate Program in Neuroscience

Research Tower
Room V-10

Thursday, July 30, 2009
10:30 am


Abstract

During the development of the nervous system, axon pathfinding is regulated by different surface-bound or secreted guidance cues. Bone morphogenic proteins (BMPs) have been shown to regulate axon pathfinding, but how they guide growth cones remains elusive. Here, I report that a BMP7 gradient elicits bidirectional turning responses from nerve growth cones. Xenopus laevis growth cones from 4-8-h cultured neurons are attracted to BMP7 gradients but become repelled by BMP7 after overnight culture. The attraction and repulsion are mediated by LIM kinase (LIMK) and Slingshot (SSH) phosphatase, respectively, which oppositely regulate the phosphorylation-dependent asymmetric activity of actin-depolymerizing factor (ADF)/cofilin to control the actin dynamics and growth cone steering. MicroRNAs are a family of 21-25bp small, non-coding RNAs that have been involved in many developmental and physiological decisions. I found that mir-134 is expressed in the dorsal part of the Xenopus spinal cord and the growth cone of spinal neuron. Overexpression or inhibition of mir-134 blocks brain-derived neurotrophic factor (BDNF) induced turning response specifically. These results suggest that mir-134 might play an important role in axon growth and pathfinding.


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