Abstract
In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.
Highlights
In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture
One is neuronal delamination by cells committed to differentiate into the neuronal lineage (mitotically active intermediate/basal progenitor (IP = BP) cells and postmitotic neurons)[2,3,4], and the other is oblique division related to the generation of outer radial glial cells2,5. oRGs are undifferentiated neural progenitor cells that divide multiple times in the subventricular zone (SVZ)
The Lzts[1] immunofluorescence signal values at the adherens junction (AJ) were negatively correlated with the values that are proportional to the circumferential length of the ZO1+AJ ring (Fig. 1i), raising the possibility that Lzts[1] has a role in delamination based on its localization to the AJ
Summary
In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. ORGs are typically produced by the oblique (or perpendicular) division of a subset of aRGs (Fig. 1a) In this case, basal daughter cells, i.e., newly generated oRGs, do not inherit the apical AJ belt and can migrate to the basal side[5,12,13,19,20], exhibiting mitotic somal translocation (MST) in which the soma rapidly translocates basally/forward before cytokinesis[6,21,22]. Basal daughter cells, i.e., newly generated oRGs, do not inherit the apical AJ belt and can migrate to the basal side[5,12,13,19,20], exhibiting mitotic somal translocation (MST) in which the soma rapidly translocates basally/forward before cytokinesis[6,21,22] These unique cellular behaviors, oblique division and MST, show evolutionary changes in their frequency and distance with relation to the size of the germinal zone in the species[20,21]. Lzts[1] is associated with microtubule components and is involved in microtubule assembly[27], further suggesting a possible function in cytoskeletal dynamics
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