Ninein is essential for the maintenance of the cortical progenitor character by anchoring the centrosome to microtubules

Abstract

SummaryThe mammalian cerebral cortex develops from proliferative apical progenitor cells (APs) that exhibit cell cycle-dependent nuclear movement (interkinetic nuclear migration; INM), which may be important for efficient and continuous production of neurons. The Pax6 transcription factor plays a major role in INM by regulating various downstream molecules. We have previously observed abnormal INM and unstable localization of the centrosome in APs of the Pax6 homozygous mutant rat embryo. To understand the mechanisms of INM, we focused on the centrosomes of APs. One of the centrosomal proteins, ninein, is specifically localized in the centrosome of APs. We observed a dramatic downregulation of ninein in APs of the Pax6 mutant. Moreover, knockdown of ninein by RNAi induced ectopic distribution of reduced numbers of BrdU-positive (S-phase) and PH3-positive (M-phase) cells. Furthermore, time-lapsed imaging demonstrated that knockdown of ninein in vivo induced abnormal INM. Finally, we observed impaired microtubule regrowth in neural progenitors taken from Pax6 homozygous mutant rat embryos, which was recovered by via ninein overexpression. We also found that ninein knockdown enlarged the surface size area of apical endfeet of the APs. Our results suggest that ninein plays a role in the molecular machinery essential for INM by connecting microtubules to the centrosome.

mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

“…Other non-ciliary effects of Kif3a or Ift88 knockout have been reported to affect microtubule dynamics, leading to spindle misorientation (Delaval et al, 2011;Kodani et al, 2013;Teng et al, 2005); ninein (Nin) + sub-distal appendages were absent from Kif3a embryonic knockout mouse fibroblasts (Kodani et al, 2013) and removal of ninein from the developing neocortex caused premature depletion of progenitors from the VZ (Wang et al, 2009) and enlargement of the endfoot area of apical progenitors (Shinohara et al, 2013). Here, no defects in subdistal appendages or ninein localization at the centrosome were detected in cilium-less RGCs at E14.5 (Fig.…”

Asymmetric inheritance of Cyclin D2 maintains proliferative neural stem/progenitor cells: A critical event in brain development and evolution

“…; Shinohara et al . ). Another important molecule located in the apical plasma membrane is prominin‐1 (CD133), which is a marker for NSPCs (Kosodo et al .…”

“…Par3, a key component of the Par protein complex, regulates the asymmetric cell division of RG cells (Bultje et al 2009). Notably, the centrosome of RG cells remains near the apical surface during most phases of the cell cycle, and centrosomal proteins such as gamma tubulin, pericentrin, and ninein are thus accumulated at the apical side (Shinohara et al 2013). The apically located centrosome seems to be important for the proper movement of the nucleus during the cell cycle (i.e., interkinetic nuclear movement) (Tamai et al 2007;Shinohara et al 2013).…”

“…Notably, the centrosome of RG cells remains near the apical surface during most phases of the cell cycle, and centrosomal proteins such as gamma tubulin, pericentrin, and ninein are thus accumulated at the apical side (Shinohara et al 2013). The apically located centrosome seems to be important for the proper movement of the nucleus during the cell cycle (i.e., interkinetic nuclear movement) (Tamai et al 2007;Shinohara et al 2013). Another important molecule located in the api-cal plasma membrane is prominin-1 (CD133), which is a marker for NSPCs (Kosodo et al 2004).…”

Neurons let it slide

“…The researchers then investigated the effect of increasing the number of unattached microtubules by knocking down the centrosomal microtubule-anchoring protein ninein (2). Partially depleting this protein enhanced microtubule sliding into the leading process, which therefore grew and took on an axon-like appearance.…”