Bidirectional multiciliated cell extrusion is controlled by Notch-driven basal extrusion and Piezo1-driven apical extrusion.

Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late-stage development, there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function.

Espin overexpression causes stereocilia defects and provides an anti-capping effect on actin polymerization.

Stereocilia are actin-based projections of hair cells that are arranged in a step like array, in rows of increasing height, and that constitute the mechanosensory organelle used for the senses of hearing and balance. In order to function properly, stereocilia must attain precise sizes in different hair cell types and must coordinately form distinct rows with varying lengths. Espins are actin-bundling proteins that have a well-characterized role in stereocilia formation; loss of function mutations in Espin result in shorter stereocilia and deafness in the jerker mouse.

Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity.

Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP-unique region of these proteins, which is essential and sufficient for ABP, includes a conserved Leucine-Rich Repeat (LRR) domain. The major binding partners of this region that could regulate ABP remain unknown.

Tubulin acetylation promotes penetrative capacity of cells undergoing radial intercalation.

Post-translational modification of tubulin provides differential functions to microtubule networks. Here, we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation, which is the process by which cells move apically, insert between outer cells, and join an epithelium. There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell.

Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells.

How cells count and regulate organelle number is a fundamental question in cell biology. For example, most cells restrict centrioles to two in number and assemble one cilium; however, multiciliated cells (MCCs) synthesize hundreds of centrioles to assemble multiple cilia. Aberration in centriole/cilia number impairs MCC function and can lead to pathological outcomes.

Ciliogenesis and autophagy are coordinately regulated by EphA2 in the cornea to maintain proper epithelial architecture.

Purpose: To understand the relationship between ciliogenesis and autophagy in the corneal epithelium.

Methods: siRNAs for EphA2 or PLD1 were used to inhibit protein expression in vitro. Morpholino-anti-EphA2 was used to knockdown EphA2 in Xenopus skin.

Building a ciliated epithelium: Transcriptional regulation and radial intercalation of multiciliated cells.

The epidermis of the Xenopus embryo has emerged as a powerful tool for studying the development of a ciliated epithelium. Interspersed throughout the epithelium are multiciliated cells (MCCs) with 100+ motile cilia that beat in a coordinated manner to generate fluid flow over the surface of the cell. MCCs are essential for various developmental processes and, furthermore, ciliary dysfunction is associated with numerous pathologies.

Overall and cause-specific survival for mucoepidermoid carcinoma of the major salivary glands: Analysis of 2210 patients.

Background: Mucoepidermoid carcinoma (MEC) is a rare malignancy of the head and neck; however, it accounts for a majority of the tumors of the salivary glands. This study used a national population-based registry to describe the pre-treatment and treatment-related prognostic factors that influence survival in patients with MEC of the major salivary glands. To our knowledge, this is the largest population-based study examining predictors of both overall and cause-specific survival of MEC of the major salivary glands.

Clinicopathologic Features and Survival Trends for Acinic Cell Carcinoma of the Major Salivary Glands: A Surveillance, Epidemiology, and End Results Population Analysis.

Background: We analyzed a population-based national registry to identify the most influential patient pretreatment and treatment factors affecting overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with acinic cell carcinoma (ACC) of the major salivary glands.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) related to survival, a total of 1,254 patients with diagnosed ACC of the major salivary glands from 1975 to 2016 met inclusion criteria. Factors significant for OS and CSS were determined using univariate and multivariate analysis with the Cox proportional hazards model.

CAMSAP3 facilitates basal body polarity and the formation of the central pair of microtubules in motile cilia.

Synchronized beating of cilia on multiciliated cells (MCCs) generates a directional flow of mucus across epithelia. This motility requires a "9 + 2" microtubule (MT) configuration in axonemes and the unidirectional array of basal bodies of cilia on the MCCs. However, it is not fully understood what components are needed for central MT-pair assembly as they are not continuous with basal bodies in contrast to the nine outer MT doublets.

Functional Architecture of Deleterious Genetic Variants in the Genome of a Wrangel Island Mammoth.

Woolly mammoths were among the most abundant cold-adapted species during the Pleistocene. Their once-large populations went extinct in two waves, an end-Pleistocene extinction of continental populations followed by the mid-Holocene extinction of relict populations on St. Paul Island ∼5,600 years ago and Wrangel Island ∼4,000 years ago.

Massive centriole production can occur in the absence of deuterosomes in multiciliated cells.

Multiciliated cells (MCCs) amplify large numbers of centrioles that convert into basal bodies, which are required for producing multiple motile cilia. Most centrioles amplified by MCCs grow on the surface of organelles called deuterosomes, whereas a smaller number grow through the centriolar pathway in association with the two parent centrioles. Here, we show that MCCs lacking deuterosomes amplify the correct number of centrioles with normal step-wise kinetics.

Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex.

The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory function of two other LAP proteins, Erbin and Lano. A combined Scrib/Erbin/Lano knockout disorganizes the cell-cell junctions and the cytoskeleton.

Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance.

Primary ciliary dyskinesia (PCD) is a genetic disorder in which impaired ciliary function leads to chronic airway disease. Exome sequencing of a PCD subject identified an apparent homozygous frameshift variant, c.887_890delTAAG (p.

CLAMP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the ciliated epithelia.

Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity.

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling.

Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium.

Subdistal Appendages Stabilize the Ups and Downs of Ciliary Life.

Centrioles acquire subdistal appendages (sDAPs) during primary cilium formation. In this issue of Developmental Cell, Mazo et al. (2016) demonstrate that sDAPs keep cilia submerged within deep membrane invaginations.

It's a family act: the geminin triplets take center stage in motile ciliogenesis.

The balance between proliferation and differentiation is a fundamental aspect of multicellular life. Perhaps nowhere is this delicate balance more palpable than in the multiciliated cells (MCCs) that line the respiratory tract, the ependyma, and the oviduct. These cells contain dozens to hundreds of motile cilia that beat in a concerted fashion to generate directed fluid flow over the tissue surface.

c21orf59/kurly Controls Both Cilia Motility and Polarization.

Cilia are microtubule-based projections that function in the movement of extracellular fluid. This requires cilia to be: (1) motile and driven by dynein complexes and (2) correctly polarized on the surface of cells, which requires planar cell polarity (PCP). Few factors that regulate both processes have been discovered.

Basal bodies in Xenopus.

Xenopus has been one of the earliest and most important vertebrate model organisms for investigating the role and structure of basal bodies. Early transmission electron microscopy studies in Xenopus revealed the fine structures of Xenopus basal bodies and their accessory structures. Subsequent investigations using multiciliated cells in the Xenopus epidermis have further revealed many important features regarding the transcriptional regulation of basal body amplification as well as the regulation of basal body/cilia polarity.

Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry.

The establishment of left-right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites-cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium.

Centriole biogenesis and function in multiciliated cells.

The use of Xenopus embryonic skin as a model system for the development of ciliated epithelia is well established. This tissue is comprised of numerous cell types, most notably the multiciliated cells (MCCs) that each contain approximately 150 motile cilia. At the base of each cilium lies the centriole-based structure called the basal body.

Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4.

Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly.

Radial intercalation is regulated by the Par complex and the microtubule-stabilizing protein CLAMP/Spef1.

The directed movement of cells is critical for numerous developmental and disease processes. A developmentally reiterated form of migration is radial intercalation; the process by which cells move in a direction orthogonal to the plane of the tissue from an inner layer to an outer layer. We use the radial intercalation of cells into the skin of Xenopus laevis embryos as a model to study directed cell migration within an epithelial tissue.