Nuclear migration during retinal development

Abstract

In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. Keywordsinterkinetic nuclear migration; nuclear translocation; nucleokinesis; neurogenesis; dynein; cell cycle; cell behavior OverviewNeuronal development is regulated by a complex array of intrinsic and extrinsic signals that act on progenitor neuroepithelial cells to ensure the correct cell type is generated in the right numbers and at the appropriate time of development (Donovan et al., 2005;Cayouette et al., 2006). In addition, multiple signaling cues are integrated in post-mitotic neuronal precursors to facilitate directed cell migration and correct laminar positioning (Malicki et al., 2004). This spatial and temporal regulation of neuronal cell-type fate commitment and histogenesis is dependent on the regulation of the mitotic cell cycle, and in particular at the level of cell cycle exit (Ohnuma and Harris, 2003). Recent data suggest that nuclear migration is a critical process for several aspects of neuronal development, including that of the neural retina. The focus of this review is on interkinetic nuclear migration and nuclear translocation during retinogenesis, although much of what we know is from observations in other regions of the developing nervous system. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Interkinetic nuclear migrationInterkinetic nuclear migration is the proliferative cell behavior where the nuclei of neuroepithelial cells migrate in an apical-basal manner and in phase with the cell cycle (Frade 2002). Neuroepithelial cell divisions are confined to apical locations while S-phase occu...

Myosin II is required for interkinetic nuclear migration of neural progenitors

“…Besides inhibiting ap3bl nuclear translocation, myosin II inhibition by low-Bb treatment also resulted in a cell fate change of neural progenitors, yielding more Tis21-GFP-and Tbr2-expressing BPs at the expense of Tis21-GFP-negative APs, and more basal mitoses at the expense of apical mitoses. It is conceivable that this cell fate change may be the consequence of the altered residence of AP nuclei in the apical versus basal region of the VZ, in line with previous proposals (4,11,14).…”

“…It has been proposed that the residence time of neural progenitor nuclei in the apical versus basal region of the VZ influences their cell fate, i.e., their proliferation versus differentiation (4,11,14). We therefore investigated whether concomitant with the impaired ap3bl nuclear translocation/ migration of neural progenitors upon low-Bb treatment, there was a shift in the proliferative versus neurogenic progenitor subpopulations.…”

“…I nterkinetic nuclear migration (INM) is a hallmark of neuroepithelial and radial glial cells, the primary stem and progenitor cells of the vertebrate CNS (1)(2)(3)(4)(5). Here, the cell nuclei migrate in concert with the progression of the cell cycle, with the cells as a whole maintaining their overall position.…”

“…In INM, the nuclei of newborn APs move away from the apical surface toward the basal lamina during G1, undergo S phase at a basal location, and return to the apical centrosomes during G2 for the next mitosis (4,5). Thus, INM is responsible for the pseudostratified appearance of the ventrical zone (VZ).…”

Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures

“…The majority of Ki67 [+] cells localized to the apical side (next to the RPE layer). Such distribution is typical for cells in the M-phase undergoing interkinetic nuclear migration in vertebrate retinogenesis [62][63][64][65][66][67]. It is also characteristic of Mstage dividing progenitors in other types of developing stratified neuroepithelia [68].…”