Defects of the fetal forebrain in mice with hereditary agenesis of the corpus callosum.

Inbred BALB/c mice are genetically the same, yet less than half of adults show absent or small corpus callosum. Is this because only a minority has prenatal defects of the sling at the telencephalic midline, or do most fetuses have a defective sling but some are able to form a corpus callosum via some other substrate pathway? This question was addressed by comparing large samples of BALB/c fetuses at 17, 18, and 19 days after conception with a series of normal C57BL/6 and hybrid fetuses matched for body size. At 17 days postconception almost all BALB/c fetuses show an unusual widening or bulge in the interhemispheric fissure anterior to the hippocampal commissure. Furthermore, formation of the hippocampal commissure is greatly retarded, although it eventually attains a normal size in adult mice. At 17 days, when mice of normal strains all have a corpus callosum at midplane, almost every BALB/c fetus lacks the structure, but 1 day later 67% of fetuses show delayed formation of this structure and by 19 days all but 7% of fetuses have some callosal axons crossing the midsagittal plane. Many BALB/c fetuses are able to form a corpus callosum without the benefit of a normal sling. The degree of delay of axon crossing is strongly correlated with the severity of sling defects. An unusually small adult corpus callosum occurs because fetal axons are able to follow unusual pathways and actively compensate for absence of the sling, not because of arrested midline development.