Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1.
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.
Lee
Alan
A
Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94141-9100, USA.
Li
Wenjun
W
Xu
Kanyan
K
Bogert
Brigitte A
BA
Su
Kimmy
K
Gao
Fen-Biao
FB
D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology / Q000254:growth & development*; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D007814:Larva / Q000254:growth & development; D009154:Mutation; D009420:Nervous System / Q000254:growth & development*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D020830:rac1 GTP-Binding Protein; C467328:FMR1 protein, Drosophila; C026452:messenger ribonucleoprotein