Role of the postnatal radial glial scaffold for the development of the dentate gyrus as revealed by reelin signaling mutant mice

Abstract

During dentate gyrus development the early embryonic radial glial scaffold is replaced by a secondary glial scaffold around birth. In contrast to neocortical and early dentate gyrus radial glial cells these postnatal glial cells are severely altered with regard to position and morphology in reeler mice lacking the secreted protein Reelin. In this study we focus on the functional impact of these defects. Most radial glial cells throughout the nervous system serve as scaffolds for migrating neurons and precursor cells for both neurogenesis and gliogenesis. Precursor cell function has been demonstrated for secondary radial glial cells but the exact function of these late glial cells in granule cell migration and positioning is not clear. No data exist concerning the interplay between granule neurons and late radial glial cells during dentate gyrus development. Here we show that despite the severe morphological defects in the reeler dentate gyrus the precursor function of secondary radial glial cells is not impaired during development in reeler mice. In addition, selective ablation of Disabled-1, an intracellular adaptor protein essential for Reelin signaling, in neurons but not in glial cells allowed us to distinguish effects of Reelin signaling on radial glial cells from possible secondary effects based on defective granule cells positioning.

RB controls growth, survival, and neuronal migration in human cerebral organoids

“…Aberrant neuronal migration was also found in Rb1-KO mice (Andrusiak et al, 2011;McClellan et al, 2007;Naser et al, 2016). This aberrant migration could be due to a disruption in the radial pattern of RGCs (Brunne et al, 2013). However, we did not find any morphological changes in the RGCs in KO organoids compared with wild-type organoids.…”

Retinoblastoma protein controls growth, survival and neuronal migration in human cerebral organoids

“…S1H). As neural progenitors use a RGC scaffold to migrate (Brunne et al, 2013) and to rule out the possibility that the aberrant positioning of Tuj1 + cells in RB1-KO organoids was due to a defect in RGC morphology, we stained sections from wild-type and RB1-KO organoids using an antibody against vimentin. However, the vimentin pattern was similar both inside and outside the tubular region in organoids from both genotypes (Fig.…”

Dab1 contributes differently to the morphogenesis of the hippocampal subdivisions

“…; Brunne et al . ). However, detailed observations using silver impregnated histological preparations were not reported.…”

“…Because neuron‐specific Dab1 KO can recapitulate the reeler phenotype of the DG (lack of hilar space) (Brunne et al . ), abnormal distribution of the intermediate progenitors in Dab1 KO is attributed to radial migration activity of the precursor cells, but involvement of abnormal development of the radial glial fibers, which is the scaffold for the radially migrating neuronal precursors toward the subgranular zone, is not still excluded. Here, we explore an alternate possibility.…”

“…Brunne et al . () reported the development of the radial glial scaffold during perinatal periods of the developing DG and its disruption in Dab1 mutants. Because neuron‐specific Dab1 KO can recapitulate the reeler phenotype of the DG (lack of hilar space) (Brunne et al .…”