Retarded growth of the medial septum: a major gene effect in acallosal mice

Abstract

Absence of the corpus callosum is a hereditary brain defect that appears with varying severity in four inbred mouse strains and is the result of more than one major genetic locus. If relatively few, perhaps two or three, loci are involved in the prenatal ontogeny of the abnormal corpus callosum, it should be possible to identify a distinct morphological process which shows a major gene effect. Because available evidence suggests the source of callosal agenesis occurs in the substrates of axon guidance near the midsagittal plane rather than in the axons themselves, morphometric analysis was done for sagittal sections of the medial septal region in embryos of normal hybrids and four acallosal strains. The anterodorsal zone of the medial septum subadjacent to the cavum septi grew much slower in acallosal BALB/c and I/LnJ mice whereas the ventral septal region was apparently normal. In the Bailey recombinant inbred strains derived from an acallosal BALB/c progenitor, one recombinant (CXBG/By) closely resembled BALB/c whereas the others resembled the normal C57BL/6 parent strain. This pattern of results supports a major gene influence on fusion of the cerebral hemispheres near the region where the corpus callosum first crosses midplane over the dorsal septum.

Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75

“…The apparent normal corpus callosum fusion in their wild type litter mates compared with our mice (Fig. 4) reinforces the possibility of strain differences between our mice (Wahlsten and Bulman-Fleming, 1994;Livy and Wahlsten, 1997). Mouse strain differences are known to have a significant impact on neuronal survival in lesion models; the C57BL/6 strain, in particular, appears to be highly invulnerable to some types of injury (Schauwecker and Steward, 1997).…”

Expression of the Netrin-1 receptor, deleted in colorectal cancer (DCC), is largely confined to projecting neurons in the developing forebrain

“…Septal defects have been shown to be associated with agenesis of the CC (Wahlsten and Bulman-Fleming, 1994), a defect seen in both the DCC and Netrin-1 mutant mice. The ventral septum is a region of high Netrin-1 mRNA expression (K.M.…”

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

“…Figure 5 shows the rate of dorsal growth of the HC during this time of gestation. The initial formation of the HC bridge occurred at the bottom of the longitudinal cerebral fissure, and by 0.600 g the gradual accumulation of axons in the HC eventually reached or surpassed the dorsal limit of the primordium of the subfornical organ just caudal to the HC (Wahlsten and Bulman-Fleming, 1994). Fusion of the hemispheres in the regions ventral and posterior to the HC appeared to be complete, but the zone directly anterior to the HC was initially filled by a loose plexus of fibers in a region that later occupied the ventral portion of the cavum septi pellucidum .…”

“…A more accurate assessment of developmental stage in the brain is provided by the body weight of the embryo (Ozaki and Wahlsten, 1992;Wahlsten and Bulman-Fleming, 1994). Figure 1 shows the approximately linear relationship between body weight and chronological age of gestation between E1 4.5 and E1 6.5 in B6D2F 2 embryos, which is similar to previous results (Ozaki and Wahlsten, 1992;Wahlsten and Bulman-Fleming, 1994). No significant difference was found in development rate between the B6D2F 2 , C129F 2 , and BALB embryos, although the C129F 2 embryos appeared to lag about half a day and the BALB embryos lagged about 1 day behind the B6D2F 2 embryos.…”

“…The mouse forebrain provides an excellent model for studying the traverse of the telencephalic midline by developing commissural axons. Inherent defects in the structure of the ventral hippocampal commissure (HC) and corpus callosum (CC) have been described in several strains of mice (Livy and Wahlsten, 1991;Ozaki and Wahlsten, 1992;Wahlsten and Bulman-Fleming, 1994), but the route taken by axons traveling through the hippocampal commissure has received little attention. These axons can first cross the midline by passing through the medial septum, over the top of the medial septum at the base of the longitudinal fissure, and have also been suggested to travel extracerebrally through the pia membrane lining the base of the longitudinal fissure (Glas, 1975).…”