Exp Mol Med.  2011 Aug;43(8):462-470. 10.3858/emm.2011.43.8.052.

JNK/stress-activated protein kinase associated protein 1 is required for early development of telencephalic commissures in embryonic brains

• Cho IH
• Lee KW
• Ha HY
• Han PL

• KMID: 1022121
• DOI: http://doi.org/10.3858/emm.2011.43.8.052

Abstract

We previously reported that mice lacking JSAP1 (jsap1-/-) were lethal and the brain of jsap1-/- at E18.5 exhibited multiple types of developmental defects, which included impaired axon projection of the corpus callosum and anterior commissures. In the current study, we examined whether the early telencephalic commissures were formed abnormally from the beginning of initial development or whether they arose normally, but have been progressively lost their maintenance in the absence of JSAP1. The early corpus callosum in the brain of jsap1+/+ at E15.5-E16.5 was found to cross the midline with forming a distinct U-shaped tract, whereas the early axonal tract in jsap1-/- appeared to cross the midline in a diffuse manner, but the lately arriving axons did not cross the midline. In the brain of jsap1-/- at E17.5, the axon terminals of lately arriving collaterals remained within each hemisphere, forming an early Probst's bundle-like shape. The early anterior commissure in the brain of jsap1+/+ at E14.5-E15.5 crossed the midline, whereas the anterior commissure in jsap1-/- developed, but was deviated from their normal path before approaching the midline. The axon tracts of the corpus callosum and anterior commissure in the brain of jsap1-/- at E16.5-E17.5 expressed phosphorylated forms of FAK and JNK, however, their expression levels in the axonal tracts were reduced compared to the respective controls in jsap1+/+. Considering the known scaffolding function of JSAP1 for the FAK and JNK pathways, these results suggest that JSAP1 is required for the pathfinding of the developing telencephalic commissures in the early brains.

Keyword

axons; focal adhesion kinase 1; JNK mitogen-activated protein kinases; MAPK8IP3 protein, human

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics/*metabolism
Animals
Brain/*embryology/*metabolism
Female
Focal Adhesion Kinase 1/genetics/metabolism
Immunohistochemistry
In Situ Nick-End Labeling
JNK Mitogen-Activated Protein Kinases/genetics/metabolism
Mice
Mice, Knockout
Nerve Tissue Proteins/genetics/*metabolism
Pregnancy
Telencephalon/*embryology/*metabolism