 |
Neuroscience Graduate Program at UCSF
Neuronal Development and Neurodegeneration
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.
Please see research summary.
Sandra Almeida
Postdoctoral Fellow
Celine Delaloy
Postdoctoral Fellow
Jacob Ferris
Research Associate
Caitlyn Gertz
NS Graduate Student
Jian Jiao
Postdoctoral Fellow
Lei Liu
Research Associate
Yubing Lu
Postdoctoral Fellow
Pankaj Sahai
BMS Graduate Student
Danqiong Sun
Postdoctoral Fellow
Xia-Lian Xu
Postdoctoral Fellow
Gao F-B. (2002). Understanding fragile X syndrome: insights from retarded flies. Neuron 34, 859–862.
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)
Gao F-B, Bogert B. (2003). Genetic control of dendritic morphogenesis in Drosophila. Trends Neurosci. 26, 262–268.
Li W, Gao F-B. (2003). Actin filament stabilizing protein tropomyosin regulates the size of dendritic fields. J. Neurosci. 23, 6171–6175.
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.
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.
Li W, Wang F, Menut L, Gao F-B. (2004). BTB/POZ-zinc finger protein Abrupt suppresses dendritic branching in a neuronal subtype-specific and dosage-dependent manner. Neuron 43, 823–834.
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.
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.
Gao F-B. (2007) Molecular and cellular mechanisms of dendritic morphogenesis. Curr. Opin. Neurobiol. 17, 525-532.
Lee J-A, Beigneux A, Ahmad ST, Young SG, Gao F-B. (2007) ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 17, 1561-1567.
Lee J-A, Gao F-B. (2008) Roles of ESCRT in autophagy-associated neurodegeneration. Autophagy 4, 230-232.
Lee J-A, Gao F-B. (2008) Regulation of Abeta pathology by beclin 1: a protective role for autophagy? J. Clin. Invest. 118, 2015-2018.
Gao F-B. (2008) Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 31, 20-26.
Delaloy C, Gao F-B. (2008) microRNA-9 multitasking near organizing centers. Nat. Neurosci. 11, 625-626.
Xu, X*, Li Y*, Wang F, Gao F-B. (2008) The steady-state level of the nervous system-specific microRNA-124a is regulated by dFMR1 in Drosophila. J. Neurosci. 28, 11883-11889.
Lu Y*, Wang F*, Li Y*, Ferris J, Lee J-A, Gao FB. (2008) The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches. Hum. Mol. Genet. Epub. Nov. 7, 2008.
Lee J-A, Gao F-B. (2008) ESCRT, autophagy, and frontotemporal dementia. BMB Reports 41, 827–832.
Lee J-A, Gao F-B. (2009) Inhibition of autophagy induction delays neuronal cell loss caused by dysfunctional ESCRT-III in frontotemporal dementia. J. Neurosci. 29, 8506–8511.
Ahmad ST, Sweeney ST, Lee J-A, Sweeney NT, Gao F-B. (2009) A genetic screen identifies Serpin5 as a regulator of the Toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc. Nat. Acad. Sci. USA. 106, 12168–12173.
Fen-Biao Gao, Ph.D.
Phone
415-734-2514
Physical Address
1650 Owens Street, Room 314
Mailing Address
Gladstone Institute of Neurological Disease
1650 Owens Street, Room 314
San Francisco, CA 94158
For Internal Campus Mail
Box 1230
Other Websites