Retarded formation of the hippocampal commissure in embryos from mouse strains lacking a corpus callosum

Abstract

A precise description of the timing and route traveled by axons traversing the telencephalic midline through the ventral hippocampal commissure (HC) is essential for understanding the role it plays in the formation of the corpus callosum (CC). A normal baseline of HC development was described in B6D2F2 hybrid mice and then compared with two inbred strains of mice displaying callosal agenesis, BALB/cWah1 (50% CC defect) and 129/J (70% CC defect), their F2 hybrid (C129F2—33% CC defect), and a recombinant inbred strain (Rl‐1—100% CC defect) derived from pairs of C129F2 mice. Embryos weighing from 0.25 g to 0.70 g (E14.5–E17) were collected and fixed by perfusion. Axon tracts were labeled using crystals of the lipophilic dyes Dil and DiA inserted into the hippocampal fimbria and cerebral cortex. HC axons in B6D2F2 mice first cross the midline at about 0.350 g body weight (E14.8) by traveling over the dorsal septum and along the pia membrane lining the longitudinal fissure. Earlier crossing was prevented by the presence of a deep cleft formed by the longitudinal fissure extending down into the septal region. Subsequent axons fasciculated along existing axons, gradually building the dorsoventral height of the HC to about 200 μm by 0.600 g. The earliest callosal axons from frontal cortex crossed the midline at 0.620 g and were clearly seen fasciculating along and between existing hippocampal axons at the dorsal surface of the HC as they crossed. In the acallosal strains, HC formation was delayed by the continued presence of the cleft deep in the septal region. This delay in time of crossing was correlated with later CC defect expression. Initial HC crossing occurred at about 0.470 g (E16.25) in BALB mice and about 0.520 g (E16.5) in 129 mice. In the Rl‐1 embryos, first HC crossing was estimated at about 0.750 g (E17.5), although several older embryos showed no crossing. These results show the importance of the HC for successful CC formation and suggest that absent CC arises as a consequence of a developmental defect which affects the formation of the hippocampal commissure prior to arrival of CC axons at midplane. Hippocampus 7:2–14, 1997. © 1997 Wiley‐Liss, Inc.

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

“…Alterations in CNPase and MBP in focal regions of the cortex may be related to the presence of Probst bundles, which have been defined as aberrant, longitudinally oriented, white matter bundles near the midline that are believed to be composed of rerouted callosal fibers [27]. Probst bundles have been previously described in BTBR mice [20] and in other mouse models of callosal agenesis (for example, netrin1 [81], NF1a [82], ddN [83], RI-I [84], Emx-1 [52]) and in human patients with partial agenesis of the corpus callosum [85]. The relationship of the small ectopic white-matter bundles in the ACC to Probst bundles is unclear, and additional experiments, such as fiber tract tracing experiments, which were historically used to define Probst bundles [86,87], may be illuminating.…”

Multiple non-cell-autonomous defects underlie neocortical callosal dysgenesis in Nfib-deficient mice

“…One possibility is that the caudal CC axons in the Nfib mutant could utilise axons of the hippocampal commissure as a substrate to cross the cortical midline [48]. Another possible determinant of CC formation in the mutant is the delayed development of midline glia within both the glial wedge and indusium griseum.…”

Early callosal absence disrupts the establishment of normal neocortical structure in Swiss mice

“…This aberrant bundle was identified bellow the ipsilateral white matter in 50% of the acallosal mice. It is important to stress that the Probst bundle is composed of callosal fibers that approach the midline but fail to cross into the contralateral hemisphere (Lent, 1984; Lent and Schmidt, 1986; Livy and Wahlsten, 1997; Meyer and Roricht, 1998; Ozaki and Wahlsten, 1993).…”