Cortical axon trajectories and growth cone morphologies in fetuses of acallosal mouse strains

Abstract

Hereditary absence of the corpus callosum (CC) provides an ideal experiment of nature for exploring mechanisms of axon guidance. In this study the prenatal development of CC axons in the acallosal mouse strains BALB/cWah1 and 129/ReJ or J was compared with normal hybrid mice by using the lipophilic dyes DiI and DiA. A few I/LnJ mice were also examined. The time of emergence and growth rate of CC axons from four cortical regions (frontal, parietal, temporal, occipital) were normal in acallosal strains. Their CC axons arrived at midplane on schedule but then often looped back to form the longitudinal Probst bundle. The frequency of formation of the Probst bundle was highest for axons from frontal cortex, which arrived at midplane first, and lowest for occipital axons, which arrived last. Once a few CC axons found a path to the other side via the hippocampal commissure, those that arrived later then crossed relatively normally. Some axons from the Probst bundle also managed to traverse midline in this manner. When no CC axons crossed, almost all of them entered the Probst bundle and eventually left it within a few hours to proceed in the ipsilateral white matter, never turning back toward midplane. Growth cones approaching midplane ipsilaterally and those that had crossed midline and entered contralateral white matter, as well as CC axons in the Probst bundle, expressed a normal range of size and complexity. These results demonstrate that the problem with callosal agenesis resides not in the cells of origin or the axons or growth cones themselves but in the substrates of axon guidance at the midsagittal plane.

Disruption of the murine nuclear factor I-A gene ( Nfia ) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum

“…However, the precise number and location of the cell bodies of neurons that pioneer the corpus callosum is still under investigation, and markers specific for this subset of neurons are not yet available (37,38,55). Furthermore, in some acallosal strains of mice it has been suggested that the inability to cross the midline may result from deficiencies in the substrates found by axonal growth cones at the midline (56). Thus the aberrant expression of genes in nonneuronal cells that are important for growth cone guidance could generate this acallosal phenotype in the Nfia Ϫ/Ϫ mice.…”

RNA-binding protein Musashi family: Roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation

“…2 E-I). In addition, a small population of msi1 Ϫ/Ϫ mice (5-10%) exhibited Probst's bundle (8), an entangled axon tract in the corpus callosum (CC), because of errors in the projection of commissural fibers across the midline in the forebrain (Fig. 2 A-D).…”

Running Wheel Accessibility Affects the Regional Electroencephalogram during Sleep in Mice

“…This interpretation is supported by recent data in mice showing that the frontal predominance of the high delta frequencies under increased sleep pressure is reduced as a result of congenital callosal dysgenesis Tobler, 2004a, 2005). In these mice callosal fibres fail to cross the midline and instead form a novel structure -the longitudinal bundle of Probst that provides redundant connectivity predominantly in the rostral portion of the neocortex (Ozaki and Shimada, 1988;Ozaki et al, 1989;Ozaki and Wahlsten, 1993). Moreover, a functional component may contribute to the hyperfrontality.…”

“…However, it is known for the rat that there are less neurons in the frontal cortex than in the posterior areas (Beaulieu, 1993). On the other hand, frontal areas receive a massive input from the contralateral cortical areas via the corpus callosum (Ozaki and Wahlsten, 1993), from the thalamus (Arbuthnott et al, 1990) and from the brainstem (Lamour et al, 1982;Woolf et al, 1983). Therefore, the relative number of synaptic connections formed in the frontal cortex may be higher compared with other areas.…”