human brain 3d model project corpus callosum

This process does not occur in naturally acallosal mammalian marsupial and monotreme species ( Gobius et al., 2016), and its failure appears to be a major cause of complete CCD in humans ( Gobius et al., 2016). IHF remodelling is mediated by intercalation of specialised astroglia, known as the midline zipper glia (MZG), across the IHF ( Silver et al., 1993 Gobius et al., 2016). We previously demonstrated that in order for callosal axons to cross the midline, the interhemispheric fissure (IHF) that separates the telencephalic hemispheres must be remodelled to form a permissive substrate ( Gobius et al., 2016). Callosal axons derived from cells within the cingulate and neocortices elongate and cross the telencephalic midline in a region of the septum termed the commissural plate ( Moldrich et al., 2010 Rakic and Yakovlev, 1968). Each of these structural phenotypes can variably impact brain function and organisation ( Brown and Paul, 2019 Edwards et al., 2014 Paul et al., 2007), but the precise developmental mechanisms that could give rise to these diverse CCD phenotypes remain unknown.ĬC formation is dependent on a prior sequence of developmental processes: cellular proliferation, migration, axonal elongation, guidance, and targeting ( Donahoo and Richards, 2009 Edwards et al., 2014 Morcom et al., 2015). CCD incorporates complete and partial congenital absence of the CC, as well as hypo- and hyperplasia (thinning or thickening, respectively) of the CC. In humans, it fails to form normally in approximately 1:4000 live births, resulting in a group of conditions collectively termed CC dysgenesis (CCD Glass et al., 2008). The corpus callosum (CC) is the largest white matter tract that mediates information transfer between brain hemispheres in placental mammals.

These findings support a model where genetic events determine corpus callosum structure by influencing leptomeningeal-astroglial interactions at the IHF. We identify an eight base-pair deletion in Draxin and misregulated astroglial and leptomeningeal proliferation as genetic and cellular factors for variable IHF remodelling and CCD in BTBR strains. We identify incomplete IHF remodelling as the key structural correlate for the range of callosal abnormalities in inbred and outcrossed BTBR mouse strains, as well as in humans with partial CCD. However, it is unclear whether defects in this process could give rise to the heterogeneity of expressivity and phenotypes seen in human cases of CCD.

Remodelling of the interhemispheric fissure (IHF) provides a substrate for callosal axons to cross between hemispheres, and its failure is the main cause of complete CCD. Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure.

Human brain 3d model project corpus callosum