A role for cingulate pioneering axons in the development of the corpus callosum

Abstract

In many vertebrate and invertebrate systems, pioneering axons play a crucial role in establishing large axon tracts. Previous studies have addressed whether the first axons to cross the midline to from the corpus callosum arise from neurons in either the cingulate cortex (Koester and O'Leary [1994] J. Neurosci. 11:6608-6620) or the rostrolateral neocortex (Ozaki and Wahlsten [1998] J. Comp. Neurol. 400:197-206). However, these studies have not provided a consensus on which populations pioneer the corpus callosum. We have found that neurons within the cingulate cortex project axons that cross the midline and enter the contralateral hemisphere at E15.5. By using different carbocyanine dyes injected into either the cingulate cortex or the neocortex of the same brain, we found that cingulate axons crossed the midline before neocortical axons and projected into the contralateral cortex. Furthermore, the first neocortical axons to reach the midline crossed within the tract formed by these cingulate callosal axons, and appeared to fasciculate with them as they crossed the midline. These data indicate that axons from the cingulate cortex might pioneer a pathway for later arriving neocortical axons that form the corpus callosum. We also found that a small number of cingulate axons project to the septum as well as to the ipsilateral hippocampus via the fornix. In addition, we found that neurons in the cingulate cortex projected laterally to the rostrolateral neocortex at least 1 day before the neocortical axons reach the midline. Because the rostrolateral neocortex is the first neocortical region to develop, it sends the first neocortical axons to the midline to form the corpus callosum. We postulate that, together, both laterally and medially projecting cingulate axons may pioneer a path for the medially directed neocortical axons, thus helping to guide these axons toward and across the midline during the formation of the corpus callosum.

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

“…As reported previously, immunolabeling of E18 forebrain tissue with anti-GFAP revealed these three glial populations, which include the indusium griseum (Ig), GW, and midline zipper glia (mzg) (Shu et al, 2003b). These studies demonstrate that the developing CC and midline structures in CD1 mice are similar to those described previously for C57BL/6 mice (Silver et al, 1993;Rash and Richards, 2001;Shu et al, 2003b).…”

“…1d-f,h). Three glial populations that have been described to function in midline guidance of CC fibers are born around E14 and have matured by E18, a time point when most or all CC fibers have crossed the midline (Rash and Richards, 2001;Shu et al, 2003b) ( Fig. 1i).…”

“…2e,f ). This expression is maintained through E17, the period at which many CC fibers have crossed the midline and extended into the contralateral hemisphere (Rash and Richards, 2001). …”

“…These studies have found EphB2 fusion protein and EphB3 mRNA expression in the CC during the development of this tract Orioli et al, 1996), which occurs between embryonic day 15 (E15) and E18 in the mouse CNS (Rash and Richards, 2001). In addition, EphA receptors were also detected in CC fibers, suggesting a possible function for these molecules in CC development (Kudo et al, 2005).…”

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

“…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). To do this we made small injections of DiI in the cingulate cortex and DiA in the neocortex.…”