The role of Pax6 in regulating the orientation and mode of cell division of progenitors in the mouse cerebral cortex

Asami, Maki; Pilz, Gregor A.; Ninkovic, Jovica; Godinho, Leanne; Schroeder, Timm; Huttner, Wieland B.; Götz, Magdalena

doi:10.1242/jcs.103960

Cited by 23 publications

(36 citation statements)

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“…However, the vast majority of radial glial cell cleavage planes in the mammalian telencephalon are perpendicular to the ventricular surface, and deviate only slightly from this angle. As a result, the apical membrane typically segregates into both daughter cells (Konno et al, 2008;Asami et al, 2011;Shitamukai et al, 2011). Therefore, it is unlikely that unequal segregation of the apical membrane accounts for IPC-and neuron-generating divisions in the mammalian cortex.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

et al. 2016

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During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development.

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Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

et al. 2016

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“…To analyze whether RGC division is affected in ephrin A5-deficient mice we performed immunostaining against Aspm to label spindle poles in combination with DAPI nuclear staining and analyzed the orientation of the cleavage plane of RGCs in relation to the ventricular surface in ephrin A5-deficient and wild-type embryos ( Fig. 2A-A″) (Fish et al, 2006;Asami et al, 2011). In accordance with Asami et al (2011), the angles of cell division were classified into three groups: with a cleavage plane of 0-30°(horizontal), 30-60°(oblique) or 60-90°(vertical) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2A-A″) (Fish et al, 2006;Asami et al, 2011). In accordance with Asami et al (2011), the angles of cell division were classified into three groups: with a cleavage plane of 0-30°(horizontal), 30-60°(oblique) or 60-90°(vertical) (Fig. 2B,B′).…”

Section: Resultsmentioning

confidence: 99%

Thalamic afferents influence cortical progenitors via ephrin A5-EphA4 interactions

et al. 2015

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The phenotype of excitatory cerebral cortex neurons is specified at the progenitor level, orchestrated by various intrinsic and extrinsic factors. Here, we provide evidence for a subcortical contribution to cortical progenitor regulation by thalamic axons via ephrin A5-EphA4 interactions. Ephrin A5 is expressed by thalamic axons and represents a high-affinity ligand for EphA4 receptors detected in cortical precursors. Recombinant ephrin A5-Fc protein, as well as ephrin A ligand-expressing, thalamic axons affect the output of cortical progenitor division in vitro. Ephrin A5-deficient mice show an altered division mode of radial glial cells (RGCs) accompanied by increased numbers of intermediate progenitor cells (IPCs) and an elevated neuronal production for the deep cortical layers at E13.5. In turn, at E16.5 the pool of IPCs is diminished, accompanied by reduced rates of generated neurons destined for the upper cortical layers. This correlates with extended infragranular layers at the expense of superficial cortical layers in adult ephrin A5-deficient and EphA4-deficient mice. We suggest that ephrin A5 ligands imported by invading thalamic axons interact with EphA4-expressing RGCs, thereby contributing to the fine-tuning of IPC generation and thus the proper neuronal output for cortical layers.

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“…Interestingly, the basal processinheriting daughter cell often acquires bRG identity and maintains self-renewal potential (Shitamukai et al, 2011;Shitamukai and Matsuzaki, 2012). However, non-vertical cleavages of mitotic aRG are rare in the embryonic mouse neocortex (Kosodo et al, 2004;Konno et al, 2008;Noctor et al, 2008;Asami et al, 2011;Shitamukai et al, 2011), which presumably accounts for the low abundance of bRG in mouse.…”

Section: Intrinsic Factors Cleavage Plane Orientationmentioning

confidence: 99%

Neural progenitors, neurogenesis and the evolution of the neocortex

2014

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The neocortex is the seat of higher cognitive functions and, in evolutionary terms, is the youngest part of the mammalian brain. Since its origin, the neocortex has expanded in several mammalian lineages, and this is particularly notable in humans. This expansion reflects an increase in the number of neocortical neurons, which is determined during development and primarily reflects the number of neurogenic divisions of distinct classes of neural progenitor cells. Consequently, the evolutionary expansion of the neocortex and the concomitant increase in the numbers of neurons produced during development entail interspecies differences in neural progenitor biology. Here, we review the diversity of neocortical neural progenitors, their interspecies variations and their roles in determining the evolutionary increase in neuron numbers and neocortex size.

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The role of Pax6 in regulating the orientation and mode of cell division of progenitors in the mouse cerebral cortex

Cited by 23 publications

References 1 publication

Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

Thalamic afferents influence cortical progenitors via ephrin A5-EphA4 interactions

Neural progenitors, neurogenesis and the evolution of the neocortex

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