Temporal dynamics of progenitor proliferation and differentiation in the developing neocortex of the plains vizcacha, Lagostomus maximus

During neocortical development, cortical expansion and gyrencephaly rely on the precise spatial and temporal regulation of neural progenitor proliferation and lineage specification. The aim of this study was to characterize progenitor cell proliferation and differentiation of the developing neocortex in Lagostomus maximus, a gyrencephalic hystricomorph with a gestation of ~155 days. Embryos of 36–134 days (e.d.) and neonates of 2 days were used. Brains (n=60) were analyzed by immunohistochemistry for Ki-67, PCNA, GFAP, Sox2 and β-III tubulin. At 35–40 e.d., PCNA+ and Ki-67+ cells were widespread throughout the neuroepithelium while between 40–60 e.d., both markers were identified in the ventricular, inner and outer subventricular zones. From 65 to 85 e.d., PCNA+ cells remained broadly distributed, whereas from 90–135 e.d. they were restricted to the cingulate cortex, with a distribution similar to GFAP. Between 43–58 e.d., Sox2+ cells predominated in the ventricular and inner subventricular zones, with few isolated cells in the outer subventricular zone; whereas from 69 e.d. to birth, they were mainly restricted to a thin ventricular layer, with scattered cells throughout the cortex. β-III tubulin+ cells were observed in the preplate at 40–45 e.d., and across cortical compartments at 45-50 e.d. These findings suggest a progressive temporal reorganization of progenitor cells, with a reduction in ventricular proliferation and subsequent neuronal and glial differentiation.