Neurons distinguish themselves from other cell types partly by their size and shape, especially their unique and often highly branched dendritic trees that remain relatively stable up to decades. Over the years, we have identified and/or characterized several key players that control different aspects of dendritic morphogenesis, including the fly homolog of human fragile X mental retardation protein 1 (dFMR1). dFMR1 is associated with the microRNA pathway. More recently we demonstrated that microRNA-9a plays a unique role in ensuring the precision of gene expression during neuronal development (Li et al., Genes Dev. 2006). We also cloned shrub, a fly gene encoding an essential component of the endosomal sorting complex required for transport (ESCRT-III) (Sweeney et al. Curr. Biol. 2006). We showed that Shrub and its mammalian homolog mSnf7-2 are involved in neuronal morphogenesis. Moreover, ESCRT-III dysfunction, either through loss of mSnf7-2 or expression of frontotemporal dementia (FTD)-associated mutant protein CHMP2BIntron5, causes autophagosome accumulation and neurodegeneration (Lee et al., Curr. Biol. 2007). These findings may have important implications for understanding FTD and other age-dependent neurodegenerative diseases.
In the near future, we will further understand how dysfunctional ESCRT-III causes neurodegeneration and its implications in the pathogenesis of FTD. We will also continue to dissect the roles of the microRNA pathway in neuronal development and in neurodevelopmental disorders.
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1. Gao F-B . (2002). Understanding fragile X syndrome: insights from retarded flies. Neuron 34, 859-862.
2. Sweeney NT*, Li W*, Gao F-B . (2002). Genetic manipulation of single neurons in vivo reveals essential roles of Flamingo in neuronal morphogenesis. Dev. Biol . 247, 76-88. (*: Equal contribution) (Featured article on the cover)
3. Gao F-B , Bogert B. (2003). Genetic control of dendritic morphogenesis in Drosophila . Trends Neurosci . 26, 262-268. (Featured article on the cover)
4. Li W, Gao F-B . (2003). Actin filament-stabilizing protein tropomyosin regulates the size of dendritic fields. J. Neurosci . 23, 6171-6175. (Featured in "This Week in the Journal")
5. Lee A, Li W, Xu K, Bogert BA, Su K, Gao F-B . (2003). Control of dendritic development by the Drosophila fragile X--related gene involves the small GTPase Rac1. Development 130, 5543-5552.
6. Xu K, Bogert BA, Li W, Su K, Lee A, Gao F-B . (2004). The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC subunit Pickpocket1. Curr. Biol . 14, 1025-1034. (Full-length article)
7. Li, W., Wang, F., Menut, L. and Gao, F-B. (2004) BTB/POZ-zinc finger
protein Abrupt regulates dendritic branching in a neuronal subtype-specific and dosage-dependent manner. Neuron 43, 823-834.
8. Sweeney NT, Brenman JE, Jan YN, Gao F-B . (2006). The coiled-coil protein Shrub controls neuronal morphogenesis in Drosophila . Curr. Biol. 16:1006-1011. (Cover story)
9. Li Y*, Wang F*, Lee J-A, Gao F-B . (2006). MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila . Genes Dev . . 20:2793-2805. (Highlighted in a "Perspective")
10. Lee J, Beigneux A, Ahmad ST, Young SG, Gao F-B. (2007). ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 17:1561-1567.
11. Gao F-B. (2007). Molecular and cellular mechanisms of dendritic morphogenesis. Curr. Opinion Neurobiol. In press.
information last updated October 2007 |
Biomedical Sciences (BMS) Graduate Program
