Differences in Mitotic Spindle Architecture in Mammalian Neural Stem Cells Influence Mitotic Accuracy during Brain Development

Abstract

Highlights d Mitotic spindle architecture changes during mammalian neurogenesis d Early-stage spindles contain more astral MTs and less spindle MTs d TPX2 loading on spindle microtubules influences spindle morphology d Spindles are more prone to chromosome segregation errors during early neurogenesis

Centrosomes: The good and the bad for brain development

“…2014; Vargas‐Hurtado et al. 2019]. This is apparently at the expense of the population of spindle MTs, which capture, align and segregate chromosomes (Figure 2B).…”

“…Accordingly, differences in the mechanisms of aRGC spindle assembly are reported between early and late stages of neurogenesis in normal brains [Vargas‐Hurtado et al. 2019] (Figure 2B). The population of astral MTs is prevalent when spindles are precisely positioned in relation to the apico–basal axis to favour vertical symmetric divisions [Mora‐Bermudez et al.…”

“…The MT‐associated protein (MAP) TPX2 appears as a key determinant in spindle architecture switch observed during neurogenesis [Vargas‐Hurtado et al. 2019]. When mitosis is challenged with drugs that affect mitotic progression, aRGCs are more prone to generate chromosome segregation errors at early stages as compared with the late stages of neurogenesis [Vargas‐Hurtado et al.…”

“…When mitosis is challenged with drugs that affect mitotic progression, aRGCs are more prone to generate chromosome segregation errors at early stages as compared with the late stages of neurogenesis [Vargas‐Hurtado et al. 2019]. Importantly, differences in spindle architecture seem to account for the observed differences in mitotic accuracy at least upon drug challenge [Vargas‐Hurtado et al.…”

“…Importantly, differences in spindle architecture seem to account for the observed differences in mitotic accuracy at least upon drug challenge [Vargas‐Hurtado et al. 2019]. It is therefore likely that the mechanisms underlying spindle assembly render aRGCs more prone to mitotic errors upon centrosome dysfunction at early as compared with the late stages of neurogenesis.…”