Synaptic Ras GTPase activating protein regulates pattern formation in the trigeminal system of mice.
The development of ordered connections or "maps" within the nervous system is a common feature of sensory systems and is crucial for their normal function. NMDA receptors are known to play a key role in the formation of these maps; however, the intracellular signaling pathways that mediate the effects of glutamate are poorly understood. Here, we demonstrate that SynGAP, a synaptic Ras GTPase activating protein, is essential for the anatomical development of whisker-related patterns in the developing somatosensory pathways in rodent forebrain. Mice lacking SynGAP show only partial segregation of barreloids in the thalamus, and thalamocortical axons segregate into rows but do not form whisker-related patches. In cortex, layer 4 cells do not aggregate to form barrels. In Syngap(+/-) animals, barreloids develop normally, and thalamocortical afferents segregate in layer 4, but cell segregation is retarded. SynGAP is not necessary for the development of whisker-related patterns in the brainstem. Immunoelectron microscopy for SynGAP from layer 4 revealed a postsynaptic localization with labeling in developing postsynaptic densities (PSDs). Biochemically, SynGAP associates with the PSD in a PSD-95-independent manner, and Psd-95(-/-) animals develop normal barrels. These data demonstrate an essential role for SynGAP signaling in the activity-dependent development of whisker-related maps selectively in forebrain structures indicating that the intracellular pathways by which NMDA receptor activation mediates map formation differ between brain regions and developmental stage.
Barnett
Mark W
MW
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Watson
Ruth F
RF
Vitalis
Tania
T
Porter
Karen
K
Komiyama
Noboru H
NH
Stoney
Patrick N
PN
Gillingwater
Thomas H
TH
Grant
Seth G N
SG
Kind
Peter C
PC
D000818:Animals; D019521:Body Patterning; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development*; D013788:Thalamus / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D014278:Trigeminal Nuclei / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C484512:Syngap1 protein, mouse; D020703:ras GTPase-Activating Proteins; D051528:Guanylate Kinases; D016283:Proto-Oncogene Proteins p21(ras)