The nervous system consists of an intricate network of neuronal connections. The formation of proper connections during development is the essential first step in building a functional nervous system. The overall goal of this study is to understand the molecular mechanisms that guide axons to find their appropriate targets. Gene targeting techniques, in vitro molecular binding experiments, and in vitro neuronal cultures will be used to study specific functional role of axon guidance molecules.
The specific aims of this proposal are: (1) to study the specific functions of plexins by analyzing the axon guidance phenotypes in plexin knockout mice, (2) to characterize the interactions of plexins by analyzing the phenotypes in double knockout mice and by studying the in vitro biochemical interactions, and (3) to explore the role of plexins in stereotyped axon pruning by analyzing the pruning phenotypes in plexin knockout mice and by establishing in vitro axonal branch pruning assays. This research will help us understand how axon guidance molecules function together to ensure that during the development of the nervous system no errors occur in the formation of the initial neuronal network. More generally, defects in forming appropriate axonal connections are likely to cause many neurodevelopmental disorders, such as autism, schizophrenia, synesthesia and mental retardation. Understanding the molecular mechanisms could revolutionize our ability to characterize and treat these developmental disorders.
| Vanderhaeghen, Pierre; Cheng, Hwai-Jong (2010) Guidance molecules in axon pruning and cell death. Cold Spring Harb Perspect Biol 2:a001859 |
| Cheng, Ting-Wen; Liu, Xiao-Bo; Faulkner, Regina L et al. (2010) Emergence of lamina-specific retinal ganglion cell connectivity by axon arbor retraction and synapse elimination. J Neurosci 30:16376-82 |
| Chen, Shih-Yu; Cheng, Hwai-Jong (2009) Functions of axon guidance molecules in synapse formation. Curr Opin Neurobiol 19:471-8 |
| Schwarz, Quenten; Waimey, Kathryn E; Golding, Matthew et al. (2008) Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development. Dev Biol 324:1-9 |
| Faulkner, Regina L; Low, Lawrence K; Liu, Xiao-Bo et al. (2008) Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling. Neural Dev 3:21 |
| Faulkner, Regina L; Jang, Mi-Hyeon; Liu, Xiao-Bo et al. (2008) Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc Natl Acad Sci U S A 105:14157-62 |
| Low, Lawrence K; Liu, Xiao-Bo; Faulkner, Regina L et al. (2008) Plexin signaling selectively regulates the stereotyped pruning of corticospinal axons from visual cortex. Proc Natl Acad Sci U S A 105:8136-41 |
| Waimey, Kathryn E; Huang, Pei-Hsin; Chen, Maggie et al. (2008) Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors. Dev Biol 315:448-58 |
| Chung, Ling; Yang, Tsung-Lin; Huang, Hsiu-Ru et al. (2007) Semaphorin signaling facilitates cleft formation in the developing salivary gland. Development 134:2935-45 |
| Faulkner, Regina L; Low, Lawrence K; Cheng, Hwai-Jong (2007) Axon pruning in the developing vertebrate hippocampus. Dev Neurosci 29:6-13 |
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