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

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.

Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation

“…Interestingly, phenotypically similar defects wherein the axonal tracts are disoriented towards rostral or caudal areas have been seen with mutants lacking allelic variations of polysialyltransferases 55 or those lacking JNK/stress-activated protein kinase-associated protein 1 (ref. 56 ). Future studies focused towards identification of additional molecules that could be expressed by the Nkx2.1-derived cells, or/and the precise mode of action of Slit2, can provide more information about the AC formation at the midline.…”

Early construction of the thalamocortical axon pathway requires c‐Jun N‐terminal kinase signaling within the ventral forebrain

“…The c-Jun N-terminal kinase (JNK) signaling pathway has been implicated in axon development, including the establishment of neuronal polarity, neurite architecture, axon guidance, and axon regeneration. [14][15][16][17][18][19] In mice, loss of Jnk1, 20 the JNK scaffolding protein JIP3, 21,22 or upstream activators of JNK signaling including DLK, 23 MKK4, 24 and MKK7, 25 lead to disruptions in the anterior commissure, corpus callosum, and internal capsule. The role of JNK in axon guidance within the Dlx5/6 territory has not yet been explored; however, our lab recently identified a novel role for JNK signaling in the migration of cortical interneurons arising from the Dlx5/6 lineage.…”

TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors

“…Immunohistochemical analyses were carried out as described previously (Cho et al, 2011). In brief, brains were perfused with 4% paraformaldehyde via a trans-cardiac method and post-fixed further in the same solution for overnight at 4 C. Brains were coronally cut at 40-mm thickness using a vibratome (Leica VT 1000S; Leica Instruments, Germany).…”