Neuronal migration prevents spatial competition in retinal morphogenesis.

The concomitant occurrence of tissue growth and organization is a hallmark of organismal development1-3. This often means that proliferating and differentiating cells are found at the same time in a continuously changing tissue environment. How cells adapt to architectural changes to prevent spatial interference remains unclear. Here, to understand how cell movements that are key for growth and organization are orchestrated, we study the emergence of photoreceptor neurons that occur during the peak of retinal growth, using zebrafish, human tissue and human organoids. Quantitative imaging reveals that successful retinal morphogenesis depends on the active bidirectional translocation of photoreceptors, leading to a transient transfer of the entire cell population away from the apical proliferative zone. This pattern of migration is driven by cytoskeletal machineries that differ depending on the direction: microtubules are exclusively required for basal translocation, whereas actomyosin is involved in apical movement. Blocking the basal translocation of photoreceptors induces apical congestion, which hampers the apical divisions of progenitor cells and leads to secondary defects in lamination. Thus, photoreceptor migration is crucial to prevent competition for space, and to allow concurrent tissue growth and lamination. This shows that neuronal migration, in addition to its canonical role in cell positioning4, can be involved in coordinating morphogenesis.

Pseudostratified epithelia - cell biology, diversity and roles in organ formation at a glance.

Pseudostratified epithelia (PSE) are widespread and diverse tissue arrangements, and many PSE are organ precursors in a variety of organisms. While cells in PSE, like other epithelial cells, feature apico-basal polarity, they generally are more elongated and their nuclei are more densely packed within the tissue. In addition, nuclei in PSE undergo interkinetic nuclear migration (IKNM, also referred to as INM), whereby all mitotic events occur at the apical surface of the elongated epithelium. Previous reviews have focused on the links between IKNM and the cell cycle, as well as the relationship between IKNM and neurogenesis, which will not be elaborated on here. Instead, in this Cell Science at a Glance article and the accompanying poster, I will discuss the cell biology of PSEs, highlighting how differences in PSE architecture could influence cellular behaviour, especially IKNM. Furthermore, I will summarize what we know about the links between apical mitosis in PSE and tissue integrity and maturation.

Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells.

Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture, and fundamental Golgi re-organization upon cell fate change.

Centriole Amplification in Zebrafish Affects Proliferation and Survival but Not Differentiation of Neural Progenitor Cells.

In animal cells, supernumerary centrosomes, resulting from centriole amplification, cause mitotic aberrations and have been associated with diseases, including microcephaly and cancer. To evaluate how centriole amplification impacts organismal development at the cellular and tissue levels, we used the in vivo imaging potential of the zebrafish. We demonstrate that centriole amplification can induce multipolar anaphase, resulting in binucleated cells. Such binucleation causes substantial apoptosis in the neuroepithelium. Interestingly, not all epithelia are similarly sensitive to binucleation, as skin cells tolerate it without entering apoptosis. In the neuroepithelium, however, binucleation leads to tissue degeneration and subsequent organismal death. Notably, this tissue degeneration can be efficiently counterbalanced by compensatory proliferation of wild-type cells. Because the risk for generating a binucleated daughter recurs at every cell division, centriole amplification in the neuroepithelium is especially deleterious during progenitor proliferation. Once cells reach the differentiation phase, however, centriole amplification does not impair neuronal differentiation.

Interkinetic nuclear migration is centrosome independent and ensures apical cell division to maintain tissue integrity.

Pseudostratified epithelia are widespread during animal development and feature elongated cells whose nuclei adopt various positions along the apicobasal cell axis. Before mitosis, nuclei migrate toward the apical surface, and subsequent divisions occur apically. So far, the exact purpose of this nuclear migration remained elusive. One hypothesis was that apical migration ensures that nuclei and centrosomes meet for mitosis. We here demonstrate that in zebrafish neuroepithelia apical nuclear migration occurs independently of centrosome position or integrity. It is a highly reproducible phenomenon linked to the cell cycle via CDK1 activity. We propose that the robustness of bringing nuclei apically for mitosis ensures that cells are capable of reintegrating into the epithelium after division. Nonapical divisions lead to cell delamination and formation of cell clusters that subsequently interfere with neuronal layering. Therefore, positioning divisions apically in pseudostratified neuroepithelia could serve to safeguard epithelial integrity and enable proper proliferation and maturation.

Mechanisms controlling arrangements and movements of nuclei in pseudostratified epithelia.

During development, cells undergo complex rearrangements that contribute to the final tissue architecture. A characteristic arrangement found in rapidly expanding, highly proliferative tissues is pseudostratified epithelium, which features notably elongated cells with varied nuclear positions along the cell axis. Although anomalies in its structure are implicated in diseases like microcephaly, how pseudostratification is formed and maintained remains elusive. In this review, we focus on a typical feature of pseudostratified epithelia called interkinetic nuclear migration (INM), which describes dynamic movements of nuclei within the elongated cell bodies. We provide an overview of cytoskeletal components underlying INM in different systems, discuss current understanding of its kinetics and timing, and evaluate how conflicting results could be explained through developmental and evolutionary considerations.