Timing and origin of the first cortical axons to project through the corpus callosum and the subsequent emergence of callosal projection cells in mouse

Abstract

A precise knowledge of the timing and origin of the first cortical axons to project through the corpus callosum (CC) and of the subsequent emergence of callosal projection cells is essential for understanding the early ontogeny of this commissure. By using a series of mouse embryos and fetuses of the hybrid cross B6D2F2/J weighing from 0.36 g to 1.0 g (embryonic day E15.75-E17.25), we examined the spatial and temporal distribution of callosal projection cells by inserting crystals of the lipophilic dye (DiI: 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) into the contralateral white matter just lateral to the midsagittal plane. Around 0.4 g or E15.8, retrogradely labeled cells were found restricted to a discrete cluster continuously distributed from the most ventral part of presumptive cingulate cortex to the hippocampus. During subsequent development, however, the tangential distribution of these labeled cells in ventromedial cortex did not extend further dorsally, and in fetuses where the CC became distinct from the hippocampal commissure (HC), labeled axons of cells in the ventral cingulate cortex were observed to intersect the callosal pathway and merge with labeled axons of the HC derived from cells in the hippocampus. The first cortical axons through the CC crossed the midline at about 0.64 g or E16.4, and these axons originated from a scattered neuronal population in the dorsal to lateral part of the presumptive frontal cortex. The earliest callosal cells were consistently located in the cortical plate and showed an immature bipolar appearance, displaying an ovoid- or pearl-shaped perikaryon with an apical dendrite coursing in a zig-zagging manner toward the pial surface and a slender axon directed toward the underlying white matter. Callosal projection cells spread progressively with development across the tangential extent of the cerebral cortex in both lateral-to-medial and rostral-to-caudal directions. In any cortical region, the first labeled cells appeared in the cortical plate and their number in the subplate was insignificant compared to that in the cortical plate. Thus, these results clarify that the CC is pioneered by frontal cortical plate cells, and the subsequent ontogeny of callosal projection cells proceeds according to the gradient of cortical maturation.

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

“…Cresyl violet-stained brain sections showed that the overall morphology of the telencephalon of jsap1 -/-at E14.5-E15.5 did not obviously differ from that of jsap1 +/+ (Figures 1A-1D; see also Figures 2-5). Our cresyl violet-stained brain sections revealed that jsap1 +/+ brains formed the CC during E15.5-E16.5 as reported previously (Koester and O'Leary, 1994;Ozaki and Wahlsten, 1998), while the early axons of the CC in the jsap1 -/-brain at E15.5-E16.5, at least in part, crossed the midline ( Figures 1C-1F). In jsap1 +/+ brains at E17.5, the axon bundle of the CC became thicker and formed a typical U-shaped tract, whereas in jsap1 -/-brains, late arriving neocortical-originated callosal axons failed to cross the midline.…”

“…In the current study, we investigated the temporal patterns of the developmental defects during the early development of jsap1 -/-brains. Previous studies reported that the early axonal extension of the CC, which stems from the cingulate cortex, pioneers across the midline of the telencephalon during E15.5-E16.5, and subsequently the late arriving collaterals originating from other regions of the neocortex join the existing tract (Koester and O'Leary, 1994;Ozaki and Wahlsten, 1998;Rash and Richards, 2001). Cresyl violet-stained brain sections showed that the overall morphology of the telencephalon of jsap1 -/-at E14.5-E15.5 did not obviously differ from that of jsap1 +/+ (Figures 1A-1D; see also Figures 2-5).…”

Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum

“…However, a recent study suggested that the cingulate axons do not pioneer the corpus callosum and instead project to the contralateral hippocampus (68). This study also suggested that the pioneering neurons for the corpus callosum were located in the rostrolateral neocortex.…”

“…The cingulate cortex sends the first axons across the cortical midline (67,68) at E17 in the rat and E15.5 in the mouse. However, a recent study suggested that the cingulate axons do not pioneer the corpus callosum and instead project to the contralateral hippocampus (68).…”

“…This study also suggested that the pioneering neurons for the corpus callosum were located in the rostrolateral neocortex. However, in both previous studies (67,68), this pathway was investigated using retrograde labeling techniques that label a single projection in isolation. Given this controversy, we decided to investigate the origin of the callosal pioneers using anterograde labeling of the axons (69).…”