Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Development 130 (22): 5543-5552


Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1

Alan Lee1, Wenjun Li1,2, Kanyan Xu1,2, Brigitte A. Bogert1,2, Kimmy Su1, and Fen-Biao Gao1,2,*

1 Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94141-9100, USA
2 Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94141-9100, USA

* Author for correspondence (e-mail: fgao{at}

Accepted for publication 11 August 2003.

Abstract: Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1 loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.

Key Words: Fragile X syndrome • Dendrites • Drosophila • Rac1

Extensive Use of RNA-Binding Proteins in Drosophila Sensory Neuron Dendrite Morphogenesis.
E. C. Olesnicky, D. J. Killian, E. Garcia, M. C. Morton, A. R. Rathjen, I. E. Sola, and E. R. Gavis (2014)
g3 4, 297-306
   Abstract »    Full Text »    PDF »
Cell-intrinsic drivers of dendrite morphogenesis.
S. V. Puram and A. Bonni (2013)
Development 140, 4657-4671
   Abstract »    Full Text »    PDF »
FMRP regulates actin filament organization via the armadillo protein p0071.
A. Nolze, J. Schneider, R. Keil, M. Lederer, S. Huttelmaier, M. M. Kessels, B. Qualmann, and M. Hatzfeld (2013)
RNA 19, 1483-1496
   Abstract »    Full Text »    PDF »
Cut, via CrebA, transcriptionally regulates the COPII secretory pathway to direct dendrite development in Drosophila.
S. C. Iyer, E. P. Ramachandran Iyer, R. Meduri, M. Rubaharan, A. Kuntimaddi, M. Karamsetty, and D. N. Cox (2013)
J. Cell Sci. 126, 4732-4745
   Abstract »    Full Text »    PDF »
Fascin controls neuronal class-specific dendrite arbor morphology.
J. Nagel, C. Delandre, Y. Zhang, F. Forstner, A. W. Moore, and G. Tavosanis (2012)
Development 139, 2999-3009
   Abstract »    Full Text »    PDF »
Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin.
M. Rosario, S. Schuster, R. Juttner, S. Parthasarathy, V. Tarabykin, and W. Birchmeier (2012)
Genes & Dev. 26, 1743-1757
   Abstract »    Full Text »    PDF »
hnRNP Q Regulates Cdc42-Mediated Neuronal Morphogenesis.
H.-H. Chen, H.-I. Yu, W.-C. Chiang, Y.-D. Lin, B.-C. Shia, and W.-Y. Tarn (2012)
Mol. Cell. Biol. 32, 2224-2238
   Abstract »    Full Text »    PDF »
Pathogenic polyglutamine proteins cause dendrite defects associated with specific actin cytoskeletal alterations in Drosophila.
S. B. Lee, J. A. Bagley, H. Y. Lee, L. Y. Jan, and Y.-N. Jan (2011)
PNAS 108, 16795-16800
   Abstract »    Full Text »    PDF »
Zipcode Binding Protein 1 Regulates the Development of Dendritic Arbors in Hippocampal Neurons.
M. Perycz, A. S. Urbanska, P. S. Krawczyk, K. Parobczak, and J. Jaworski (2011)
J. Neurosci. 31, 5271-5285
   Abstract »    Full Text »    PDF »
Differential Regulation of Dendritic and Axonal Development by the Novel Kruppel-Like Factor Dar1.
B. Ye, J. H. Kim, L. Yang, I. McLachlan, S. Younger, L. Y. Jan, and Y. N. Jan (2011)
J. Neurosci. 31, 3309-3319
   Abstract »    Full Text »    PDF »
Fragile X Mental Retardation Protein Regulates New Neuron Differentiation in the Adult Olfactory Bulb.
S. Scotto-Lomassese, A. Nissant, T. Mota, M. Neant-Fery, B. A. Oostra, C. A. Greer, P.-M. Lledo, A. Trembleau, and I. Caille (2011)
J. Neurosci. 31, 2205-2215
   Abstract »    Full Text »    PDF »
FMRP Regulates the Transition from Radial Glial Cells to Intermediate Progenitor Cells during Neocortical Development.
R. Saffary and Z. Xie (2011)
J. Neurosci. 31, 1427-1439
   Abstract »    Full Text »    PDF »
Fragile X syndrome and model organisms: identifying potential routes of therapeutic intervention.
B. Bhogal and T. A. Jongens (2010)
Dis. Model. Mech. 3, 693-700
   Abstract »    Full Text »    PDF »
Short- and Long-Term Memory Are Modulated by Multiple Isoforms of the Fragile X Mental Retardation Protein.
P. Banerjee, B. P. Schoenfeld, A. J. Bell, C. H. Choi, M. P. Bradley, P. Hinchey, M. Kollaros, J. H. Park, S. M. J. McBride, and T. C. Dockendorff (2010)
J. Neurosci. 30, 6782-6792
   Abstract »    Full Text »    PDF »
Astrocytes Prevent Abnormal Neuronal Development in the Fragile X Mouse.
S. Jacobs and L. C. Doering (2010)
J. Neurosci. 30, 4508-4514
   Abstract »    Full Text »    PDF »
The State of Synapses in Fragile X Syndrome.
B. E. Pfeiffer and K. M. Huber (2009)
Neuroscientist 15, 549-567
   Abstract »    PDF »
Fragile X syndrome: from molecular genetics to therapy.
C D'Hulst and R F Kooy (2009)
J. Med. Genet. 46, 577-584
   Abstract »    Full Text »    PDF »
Genetic Modifiers of dFMR1 Encode RNA Granule Components in Drosophila.
A.-M. J. Cziko, C. T. McCann, I. C. Howlett, S. A. Barbee, R. P. Duncan, R. Luedemann, D. Zarnescu, K. E. Zinsmaier, R. R. Parker, and M. Ramaswami (2009)
Genetics 182, 1051-1060
   Abstract »    Full Text »    PDF »
The Steady-State Level of the Nervous-System-Specific MicroRNA-124a Is Regulated by dFMR1 in Drosophila.
X.-L. Xu, Y. Li, F. Wang, and F.-B. Gao (2008)
J. Neurosci. 28, 11883-11889
   Abstract »    Full Text »    PDF »
Drosophila Fragile X Mental Retardation Protein and Metabotropic Glutamate Receptor A Convergently Regulate the Synaptic Ratio of Ionotropic Glutamate Receptor Subclasses.
L. Pan and K. S. Broadie (2007)
J. Neurosci. 27, 12378-12389
   Abstract »    Full Text »    PDF »
Fragile X mental retardation protein modulates the fate of germline stem cells in Drosophila.
L. Yang, R. Duan, D. Chen, J. Wang, D. Chen, and P. Jin (2007)
Hum. Mol. Genet. 16, 1814-1820
   Abstract »    Full Text »    PDF »
Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice.
M. L. Hayashi, B. S. S. Rao, J.-S. Seo, H.-S. Choi, B. M. Dolan, S.-Y. Choi, S. Chattarji, and S. Tonegawa (2007)
PNAS 104, 11489-11494
   Abstract »    Full Text »    PDF »
Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation.
B. Ramos, B. Gaudilliere, A. Bonni, and G. Gill (2007)
PNAS 104, 9882-9887
   Abstract »    Full Text »    PDF »
Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites.
J. Z. Parrish, K. Emoto, L. Y. Jan, and Y. N. Jan (2007)
Genes & Dev. 21, 956-972
   Abstract »    Full Text »    PDF »
Fragile X Mental Retardation Protein Induces Synapse Loss through Acute Postsynaptic Translational Regulation.
B. E. Pfeiffer and K. M. Huber (2007)
J. Neurosci. 27, 3120-3130
   Abstract »    Full Text »    PDF »
Substitution of Critical Isoleucines in the KH Domains of Drosophila Fragile X Protein Results in Partial Loss-of-Function Phenotypes.
P. Banerjee, S. Nayar, S. Hebbar, C. F. Fox, M. C. Jacobs, J. H. Park, J. J. Fernandes, and T. C. Dockendorff (2007)
Genetics 175, 1241-1250
   Abstract »    Full Text »    PDF »
Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome.
B. Tucker, R. I. Richards, and M. Lardelli (2006)
Hum. Mol. Genet. 15, 3446-3458
   Abstract »    Full Text »    PDF »
Fragile X mental retardation protein controls trailer hitch expression and cleavage furrow formation in Drosophila embryos.
K. Monzo, O. Papoulas, G. T. Cantin, Y. Wang, J. R. Yates III, and J. C. Sisson (2006)
PNAS 103, 18160-18165
   Abstract »    Full Text »    PDF »
MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila.
Y. Li, F. Wang, J.-A Lee, and F.-B. Gao (2006)
Genes & Dev. 20, 2793-2805
   Abstract »    Full Text »    PDF »
Ral Is both Necessary and Sufficient for the Inhibition of Myeloid Differentiation Mediated by Ras.
N. Omidvar, L. Pearn, A. K. Burnett, and R. L. Darley (2006)
Mol. Cell. Biol. 26, 3966-3975
   Abstract »    Full Text »    PDF »
Control of Dendritic Arborization by the Phosphoinositide-3'-Kinase-Akt-Mammalian Target of Rapamycin Pathway.
J. Jaworski, S. Spangler, D. P. Seeburg, C. C. Hoogenraad, and M. Sheng (2005)
J. Neurosci. 25, 11300-11312
   Abstract »    Full Text »    PDF »
Calcium/Calmodulin-Dependent Protein Kinase II Alters Structural Plasticity and Cytoskeletal Dynamics in Drosophila.
R. Andersen, Y. Li, M. Resseguie, and J. E. Brenman (2005)
J. Neurosci. 25, 8878-8888
   Abstract »    Full Text »    PDF »
FMRP interferes with the Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts.
M. Castets, C. Schaeffer, E. Bechara, A. Schenck, E. W. Khandjian, S. Luche, H. Moine, T. Rabilloud, J.-L. Mandel, and B. Bardoni (2005)
Hum. Mol. Genet. 14, 835-844
   Abstract »    Full Text »    PDF »
Protein Expression Profiling of the Drosophila Fragile X Mutant Brain Reveals Up-regulation of Monoamine Synthesis.
Y. Q. Zhang, D. B. Friedman, Z. Wang, E. Woodruff III, L. Pan, J. O'Donnell, and K. Broadie (2005)
Mol. Cell. Proteomics 4, 278-290
   Abstract »    Full Text »    PDF »
Visual Experience Regulates Transient Expression and Dendritic Localization of Fragile X Mental Retardation Protein.
L. A. Gabel, S. Won, H. Kawai, M. McKinney, A. M. Tartakoff, and J. R. Fallon (2004)
J. Neurosci. 24, 10579-10583
   Abstract »    Full Text »    PDF »
Defective Neuronal Development in the Mushroom Bodies of Drosophila Fragile X Mental Retardation 1 Mutants.
C. I. Michel, R. Kraft, and L. L. Restifo (2004)
J. Neurosci. 24, 5798-5809
   Abstract »    Full Text »    PDF »
Molecular and Comparative Genetics of Mental Retardation.
J. K. Inlow and L. L. Restifo (2004)
Genetics 166, 835-881
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882