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Figure 9


Fig. 9. Comparison of the C3Ggt/gt mutant phenotype with the Reeler phenotype and the nervous-system-specific β1 integrin conditional mutant phenotype. (A) At E14.5, the developing wild-type mouse cortex consists of ventricular (VZ), subventricular (SVZ) and intermediate (IZ) zones, subplate (SP), the nascent cortical plate (CP), marginal zone (MZ) and has a continuous basement membrane (BM) at its pial surface. Cajal-Retzius (CR, green) cells expressing reelin are located in the marginal zone. Radial glial processes (RGP) extend from the ventricular zone to the basement membrane at the pial surface, where they are anchored with endfeet to the extracellular matrix protein lattice. Migrating bipolar neurons (biN) are guided by radial glial processes and may transiently become multipolar (muN). (B) β1 integrin deficiency in the brain leads to a disruption of the basement membrane, loss of parallel radial glial process orientation and loss of endfeet anchoring, as well as an undulating cortical plate (U-CP) with invasion of the marginal zone by cortical plate cells (Graus-Porta et al., 2001). (C) Loss of reelin leads to a lack of reelin expression in the Cajal-Retzius cells and to a failure of cortical plate cells to split the preplate (PP) into marginal zone and subplate, resulting in an unsplit preplate (US-PP) and the stacking of cortical plate cells (CPC) below the unsplit preplate (Sheppard and Pearlman, 1997). In addition, lack of reelin leads to oblique orientation of the radial glial processes. (D) The C3Ggt/gt mutant phenotype combines all elements of the Reeler phenotype and the β1 integrin mutant phenotype: lack of preplate splitting, the stacking of cortical plate cells below the unsplit preplate, disruption of the basement membrane, invasion of the marginal zone and pericerebral space by cortical plate cells, loss of radial glial process orientation and loss of endfeet anchoring. In addition, lack of C3G leads to an accumulation of migrating neurons in the multipolar stage.





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