Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex

Abstract

BackgroundDuring the development of the mammalian cerebral cortex, newborn postmitotic projection neurons are born from local neural stem cells and must undergo radial migration so as to position themselves appropriately to form functional neural circuits. The zinc finger transcriptional repressor Rp58 (also known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its underlying molecular mechanism remains to be better characterised.FindingsHere, we demonstrate that the co-expression of Rp58 and the cyclin dependent kinase inhibitor (CDKI) p27kip1 is important for E14.5-born cortical neurons to coordinate cell cycle exit and initiate their radial migration. Notably, we find that the impaired radial positioning of Rp58-deficient cortical neurons within the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar transition from the intermediate zone to the cortical plate can be restored by forced expression of p27kip1 in concert with suppression of Rnd2, a downstream target gene of Rp58. Furthermore, the restorative effects of p27kip1 and Rnd2 abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient cells.ConclusionsOur findings demonstrate functional interplay between a transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit, as well as to promote radial migration through a molecular mechanism consistent with suppression of RhoA signalling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-017-0084-3) contains supplementary material, which is available to authorized users.

Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins

“…Gene inactivation by a knockout approach has demonstrated that RP58 plays a crucial role in neuronal proliferation, migration, and differentiation in the developing cerebral cortex, as well as regulation of embryonic myogenesis . Further analyses showed that Id (inhibitor of differentiation) genes are direct targets of RP58 .…”

“…Gene inactivation by a knockout approach has demonstrated that RP58 plays a crucial role in neuronal proliferation, migration, and differentiation in the developing cerebral cortex, as well as regulation of embryonic myogenesis. [48][49][50][51][52][53][54] Further analyses showed that Id (inhibitor of differentia-tion) genes are direct targets of RP58. 54,55 Protein structure analysis revealed that RP58 contains an extensively conserved region at the amino terminus, termed the BTB/POZ domain, and Kruppeltype zinc finger motifs in the carboxyl-terminal region.…”

Visualizing Cell Cycle Phase Organization and Control During Neural Lineage Elaboration

“…of its maximum area. Therefore, we calculated the fluorescence intensity in fluorescence units (FU) as (integrated fluorescent intensity/area) [14] for comparative measurements. Statistical analyses were carried out using Prism 6 (GraphPad, San Diego, CA, USA).…”

“…FU-average intensity in fluorescence units. (E) Box plots showing p27 KIP1 levels by cell cycle phase for NSCs and IPCs (n = 185, 13,50,7,72,13,149,14). In plotting these graphs, we combine cells in G2 with the small percentage of cells (2% in NSCs and In proliferating cells, the relatively slow rate at which a FP-hCdt1 (30/120) protein matures means this marker is active at a weak level at the initiation of G1 phase, then increases as the cell proceeds through G1.…”

Correction to: Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex

“…After publication of the original article [ 1 ] it was realised that there were errors in figures 2a,b,f,g, which arose as a result of preparing figures from data collected and analysed at the same time as the work reported in [ 2 ] (Supplementary Figure 1 of [ 2 ]).…”