Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3).
The murine JNK-interacting protein 3 (JIP3) protein (also known as JSAP1) is expressed exclusively in neurons and has been identified as a scaffold protein for the c-Jun NH2-terminal kinase (JNK) signaling pathway and as an adapter protein for cargo transport by the microtubule motor protein kinesin. To investigate the physiological function of JIP3, we examined the effect of Jip3 gene disruption in mice. The Jip3-/- mice were unable to breathe and died shortly after birth. Microscopic analysis demonstrated that Jip3 gene disruption causes severe defects in the morphogenesis of the telencephalon. Jip3-/- mice lack the telencephalic commissure, a major connection between the left and right hemispheres of the brain. The central nervous system abnormalities of Jip3-/- mice may be accounted for in part by a reduction in signal transduction by RhoA and its effector ROCK.
Kelkar
Nyaya
N
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Delmotte
Marie-Helene
MH
Weston
Claire R
CR
Barrett
Tamera
T
Sheppard
Barbara J
BJ
Flavell
Richard A
RA
Davis
Roger J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D015398:Signal Transduction; D013687:Telencephalon / Q000002:abnormalities / Q000196:embryology*; D033921:Vesicular Transport Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein