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PMID: 17224404 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development.

Neuron ·Vol. 53 ·No. 2 ·2007-01-18 ·Pages 217-32

Paradis S, Harrar DB, Lin Y, Koon AC, Hauser JL, Griffith EC, Zhu L, Brass LF, Chen C, Greenberg ME

Abstract

We report the results of a genetic screen to identify molecules important for synapse formation and/or maintenance. siRNAs were used to decrease the expression of candidate genes in neurons, and synapse development was assessed. We surveyed 22 cadherin family members and demonstrated distinct roles for cadherin-11 and cadherin-13 in synapse development. Our screen also revealed roles for the class 4 Semaphorins Sema4B and Sema4D in the development of glutamatergic and/or GABAergic synapses. We found that Sema4D affects the formation of GABAergic, but not glutamatergic, synapses. Our screen also identified the activity-regulated small GTPase Rem2 as a regulator of synapse development. A known calcium channel modulator, Rem2 may function as part of a homeostatic mechanism that controls synapse number. These experiments establish the feasibility of RNAi screens to characterize the mechanisms that control mammalian neuronal development and to identify components of the genetic program that regulate synapse formation and/or maintenance.

MeSH Terms
Animals Cadherins/physiology Feasibility Studies Glutamic Acid/metabolism Humans Molecular Biology Monomeric GTP-Binding Proteins/physiology Nerve Tissue Proteins/physiology RNA Interference RNA, Small Interfering Semaphorins/classification,physiology Synapses/physiology gamma-Aminobutyric Acid/metabolism
Chemicals
Cadherins H-cadherin Nerve Tissue Proteins RNA, Small Interfering Semaphorins osteoblast cadherin Glutamic Acid gamma-Aminobutyric Acid Monomeric GTP-Binding Proteins Rem2 protein, mouse
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Paradis Suzanne
Neurobiology Program, Department of Neurology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
Harrar Dana B
Lin Yingxi
Koon Alex C
Hauser Jessica L
Griffith Eric C
Zhu Li
Brass Lawrence F
Chen Chinfei
Greenberg Michael E
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/j.neuron.2006.12.012
Published
2007-01-18
Pages
217-32
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC1950560
Subset
IM
Grants
NHLBI NIH HHS · HL81012 · United States
NEI NIH HHS · R01 EY013613 · United States
NICHD NIH HHS · P30 HD018655-25 · United States
NINDS NIH HHS · NS45500 · United States
NINDS NIH HHS · R01 NS045500 · United States
NICHD NIH HHS · P30 HD018655 · United States
NICHD NIH HHS · HD18655 · United States
NINDS NIH HHS · R01 NS045500-20 · United States
NHLBI NIH HHS · P50 HL081012 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2006.12.012 PMC Full Text View journal details
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