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Polarized epithelia are a foundation of organ and appendage structures throughout Metazoa and serve as a physical barrier to preserve physiological functions. In proliferating epithelia, planar cell division occurs by orienting the mitotic spindle within the plane of the epithelium to ensure tissue organization. Conversely, loss of tissue architecture is a hallmark of carcinoma, and aberrant spindle orientation is hypothesized to contribute to tissue disorganization through dysplasia and cell dissemination. Recent in vivo studies have uncovered a role of planar spindle alignment in the robust maintenance of tissue architecture, which accompanies homeostatic mechanisms such as cell delamination and re-integration of misplaced cells following abnormal cell division. Furthermore, perpendicular spindle orientation shifts have been suggested as causes of cell fate change and epithelial plasticity manifested by epithelial-to-mesenchymal transition. This review describes the mechanism by which planar spindle orientation is tightly regulated and discusses the roles of mitotic spindle orientation in epithelial development and disease. [ABSTRACT FROM AUTHOR]

During epithelial cell proliferation, planar alignment of the mitotic spindle coordinates the local process of symmetric cell cleavage with the global maintenance of polarized tissue architecture. Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer, the in vivo mechanisms regulating mitotic spindle orientation remain elusive. Here we demonstrate that the actomyosin cortex and the junction-localized neoplastic tumour suppressors Scribbled and Discs large 1 have essential roles in planar spindle alignment and thus the control of epithelial integrity in the Drosophila imaginal disc. We show that defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and that blocking the death of misaligned cells is sufficient to drive the formation of basally localized tumour-like masses. These findings indicate a key role for junction-mediated spindle alignment in the maintenance of epithelial integrity, and also reveal a previously unknown cell-death-mediated tumour-suppressor function inherent in the polarized architecture of epithelia. [ABSTRACT FROM AUTHOR]

Background: The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes. Results: Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions. Conclusions: These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals. [ABSTRACT FROM AUTHOR]

The Scrib module proteins, Scrib, Dlg, and Lgl, are conserved regulators of cell polarity in diverse biological contexts. Originally discovered as neoplastic tumor suppressors in the fruit fly Drosophila melanogaster , disruption of Scrib module components leads to tumorigenesis in mammalian epithelia and is associated with human cancers. With multiple protein interacting domains, Scrib module proteins function as determinants of basolateral identity in epithelial cells with apical-basal polarity while acting as signaling platform scaffold proteins. Recent studies have further revealed novel roles of the Scrib module in the control of epithelial architecture, ranging from polarity establishment and tricellular junction formation to planar spindle orientation during cell division. This review updates the current understanding of the molecular nature and physiological functions of the Scrib module with a focus on in vivo studies, providing a framework for how these protein dynamics affect the processes of epithelial organization. [ABSTRACT FROM AUTHOR]

Blastema formation is a crucial process that provides a cellular source for regenerating tissues and organs. While bilaterians have diversified blastema formation methods, its mechanisms in non-bilaterians remain poorly understood. Cnidarian jellyfish, or medusae, represent early-branching metazoans that exhibit complex morphology and possess defined appendage structures highlighted by tentacles with stinging cells (nematocytes). Here, we investigate the mechanisms of tentacle regeneration, using the hydrozoan jellyfish Cladonema pacificum. We show that proliferative cells accumulate at the tentacle amputation site and form a blastema composed of cells with stem cell morphology. Nucleoside pulse-chase experiments indicate that most repair-specific proliferative cells (RSPCs) in the blastema are distinct from resident stem cells. We further demonstrate that resident stem cells control nematogenesis and tentacle elongation during both homeostasis and regeneration as homeostatic stem cells, while RSPCs preferentially differentiate into epithelial cells in the newly formed tentacle, analogous to lineage-restricted stem/progenitor cells observed in salamander limbs. Taken together, our findings propose a regeneration mechanism that utilizes both resident homeostatic stem cells (RHSCs) and RSPCs, which in conjunction efficiently enable functional appendage regeneration, and provide novel insight into the diversification of blastema formation across animal evolution. Jellyfish are known for their remarkable regenerative abilities. This study shows that in the jellyfish Cladonema, following tentacle amputation, repair-specific proliferating cells robustly form a blastema with stem-like properties; these are distinct from resident stem cells and have a preference for differentiating into epithelial cells. [ABSTRACT FROM AUTHOR]

Summary Widely implicated in human disease, abnormal cellular cysts reflect dramatic defects in the maintenance of epithelial integrity. A new study reports that epithelial cysts may arise as a surprisingly general consequence of clonal defects in the specification of cell identity. [ABSTRACT FROM AUTHOR]

Summary The Drosophila neoplastic tumor suppressor Lethal giant larvae (Lgl) regulates apico–basal polarity in epithelia as well as the asymmetric segregation of cell fate in neural progenitors. Two new studies uncover a new facet of its regulation in epithelia, where Aurora-dependent phosphorylation triggers Lgl dissociation from the basolateral cortex to facilitate planar orientation of the mitotic spindle. [ABSTRACT FROM AUTHOR]

Patient-derived xenograft (PDX) is an emerging tool established in immunodeficient vertebrate models to assess individualized treatments for cancer patients. Current xenograft models are deficient in adaptive immune systems. However, the precise role of the innate immunity in the xenograft models is unknown. With conserved signaling pathways and established genetic tools, Drosophila has contributed to the understanding of the mechanism of tumor growth as well as tumor–host interactions for decades, making it a promising candidate model for studying whether or not the hosts' innate immunity can accommodate transplanted human tumor cells. Here we show initial observations that assess the behavior and impact of several human tumor cell lines when transplanted into Drosophila. We found that some injected cell lines persisted for a longer duration and reduced hosts' lifespan. In particular, the human lung cancer cell line A549 were observed adjacent to the fly host tissues. We examined two factors that affect the survivability of cancer cells: (1) the optimal temperature of each cell line and (2) the innate immunity of Drosophila hosts. Especially, transplanted human tumor cells survived longer in immunodeficient flies, suggesting that the host innate immune system impedes the growth of xenografted cells. Our attempts for xenografting fly models thus provide necessary steps to overcome for establishing PDX cancer models using invertebrates. [ABSTRACT FROM AUTHOR]

An abstract of the article "Nonautonomous Apoptosis Is triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila," by Yu-ichiro Nakajima, Erina Kuranaga, Kaoru Sugimura, Atsushi Miyawaki and Masayuki Miura, is presented.

As the sister group to bilaterians, cnidarians stand in a unique phylogenetic position that provides insight into evolutionary aspects of animal development, physiology, and behavior. While cnidarians are classified into two types, sessile polyps and free-swimming medusae, most studies at the cellular and molecular levels have been conducted on representative polyp-type cnidarians and have focused on establishing techniques of genetic manipulation. Recently, gene knockdown by delivery of short hairpin RNAs into eggs via electroporation has been introduced in two polyp-type cnidarians, Nematostella vectensis and Hydractinia symbiolongicarpus, enabling systematic loss-of-function experiments. By contrast, current methods of genetic manipulation for most medusa-type cnidarians, or jellyfish, are quite limited, except for Clytia hemisphaerica, and reliable techniques are required to interrogate function of specific genes in different jellyfish species. Here, we present a method to knock down target genes by delivering small interfering RNA (siRNA) into fertilized eggs via electroporation, using the hydrozoan jellyfish, Clytia hemisphaerica and Cladonema paciificum. We show that siRNAs targeting endogenous GFP1 and Wnt3 in Clytia efficiently knock down gene expression and result in known planula phenotypes: loss of green fluorescence and defects in axial patterning, respectively. We also successfully knock down endogenous Wnt3 in Cladonema by siRNA electroporation, which circumvents the technical difficulty of microinjecting small eggs. Wnt3 knockdown in Cladonema causes gene expression changes in axial markers, suggesting a conserved Wnt/β-catenin-mediated pathway that controls axial polarity during embryogenesis. Our gene-targeting siRNA electroporation method is applicable to other animals, including and beyond jellyfish species, and will facilitate the investigation and understanding of myriad aspects of animal development. [ABSTRACT FROM AUTHOR]

Medusozoans, the Cnidarian subphylum, have multiple life stages including sessile polyps and free-swimming medusae or jellyfish, which are typically bell-shaped gelatinous zooplanktons that exhibit diverse morphologies. Despite having a relatively complex body structure with well-developed muscles and nervous systems, the adult medusa stage maintains a high regenerative ability that enables organ regeneration as well as whole body reconstitution from the part of the body. This remarkable regeneration potential of jellyfish has long been acknowledged in different species; however, recent studies have begun dissecting the exact processes underpinning regeneration events. In this article, we introduce the current understanding of regeneration mechanisms in medusae, particularly focusing on cellular behaviors during regeneration such as wound healing, blastema formation by stem/progenitor cells or cell fate plasticity, and the organism-level patterning that restores radial symmetry. We also discuss putative molecular mechanisms involved in regeneration processes and introduce a variety of novel model jellyfish species in the effort to understand common principles and diverse mechanisms underlying the regeneration of complex organs and the entire body. [ABSTRACT FROM AUTHOR]