An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development.
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.
Paradis
Suzanne
S
Neurobiology Program, Department of Neurology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
Harrar
Dana B
DB
Lin
Yingxi
Y
Koon
Alex C
AC
Hauser
Jessica L
JL
Griffith
Eric C
EC
Zhu
Li
L
Brass
Lawrence F
LF
Chen
Chinfei
C
Greenberg
Michael E
ME
D000818:Animals; D015820:Cadherins / Q000502:physiology; D005240:Feasibility Studies; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008967:Molecular Biology; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D039961:Semaphorins / Q000145:classification / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015820:Cadherins; C099972:H-cadherin; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D039961:Semaphorins; C086960:osteoblast cadherin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020559:Monomeric GTP-Binding Proteins; C517391:Rem2 protein, mouse