Arp2/3 networks, commonly, interact with discrete actin assemblies, constructing extensive combinations that function in conjunction with contractile actomyosin networks to engender whole-cell responses. This review investigates these tenets by drawing upon examples of Drosophila development. The polarized assembly of supracellular actomyosin cables, which constrict and reshape epithelial tissues in the context of embryonic wound healing, germ band extension, and mesoderm invagination, is our initial focus. These cables also serve as physical dividers between tissue compartments at parasegment boundaries and during dorsal closure. Subsequently, we investigate how locally formed Arp2/3 networks work against actomyosin structures during myoblast cell fusion and the embryonal syncytium's cortical organization, and how these networks likewise cooperate in individual hemocyte migration and the coordinated migration of border cells. Through these examples, the influence of polarized actin network deployment and its higher-order interactions on the organization and progression of developmental cell biology is strikingly apparent.
Before hatching, the Drosophila egg already possesses its two essential body axes and is replete with the necessary sustenance to become a self-sufficient larva within just 24 hours. Unlike the creation of an egg cell from a female germline stem cell, a complex process known as oogenesis, which takes approximately a week. ML 210 mw Key symmetry-breaking events driving Drosophila oogenesis will be discussed, including the polarization of both body axes, the asymmetric division of germline stem cells, the selection of the oocyte from the 16-cell cyst, its positioning at the cyst's posterior, Gurken signaling from the oocyte to polarize the follicle cell epithelium's anterior-posterior axis surrounding the developing germline cyst, reciprocal signaling from posterior follicle cells to polarize the oocyte's anterior-posterior axis, and the migratory specification of the dorsal-ventral axis by the oocyte nucleus. Due to the sequential nature of each event, establishing the preconditions for the next, I will concentrate on the mechanisms that activate these symmetry-breaking steps, their connections, and the outstanding queries.
Epithelial tissues display a multitude of morphologies and roles across metazoan organisms, from broad sheets surrounding internal organs to intricate tubes facilitating the absorption of nutrients, all of which necessitate the establishment of apical-basolateral polarity. Although the underlying principle of component polarization is common to all epithelial cells, the actual implementation of this polarization process varies significantly depending on the tissue's unique characteristics, likely influenced by developmental specificities and the diverse functions of polarizing cell lineages. In biological research, the nematode Caenorhabditis elegans, or C. elegans, plays a critical role as a model organism. Caenorhabditis elegans's outstanding imaging and genetic resources, coupled with its distinctive epithelia, whose origins and roles are well-understood, make it a premier model organism for studying polarity mechanisms. This review underscores the interplay of epithelial polarization, development, and function by focusing on symmetry breaking and polarity establishment within the C. elegans intestine, a well-characterized model. The polarization patterns of the C. elegans intestine are examined in relation to the polarity programs of the pharynx and epidermis, seeking to correlate varied mechanisms with tissue-specific distinctions in geometry, embryonic origins, and functions. We emphasize the importance of researching polarization mechanisms, focusing on each tissue's unique characteristics, while simultaneously underscoring the benefits of inter-tissue comparisons of polarity.
A stratified squamous epithelium, namely the epidermis, comprises the outermost layer of the skin. A crucial aspect of its function is acting as a barricade, keeping pathogens and toxins at bay, and regulating moisture retention. The tissue's physiological function necessitates substantial differences in its organization and polarity, setting it apart from simple epithelial tissues. Four aspects of polarity in the epidermis are considered: the distinct polarity of basal progenitor cells and differentiated granular cells, the alteration in polarity of cellular adhesions and the cytoskeleton as keratinocytes differentiate throughout the tissue, and the planar polarity of the tissue. These distinct polarities are paramount to the development and proper operation of the epidermis and are also significantly implicated in the regulation of tumor formation.
A multitude of cells composing the respiratory system form complex, branched airways, ending at the alveoli. These alveoli are essential for guiding air and facilitating gas exchange with the circulatory system. Lung morphogenesis and the establishment of respiratory system structure are guided by distinct forms of cellular polarity, which are also responsible for creating a defensive barrier against microbes and toxins. Cell polarity's crucial role is observed in the regulation of the stability of lung alveoli, luminal surfactant and mucus secretion in airways, and the coordinated motion of multiciliated cells that generate proximal fluid flow, defects in which contribute to respiratory disease pathogenesis. We encapsulate the existing information on cellular polarity within lung development and homeostasis, emphasizing the critical functions of polarity in alveolar and airway epithelial cells, and its association with microbial infections and diseases such as cancer.
Epithelial tissue architecture undergoes extensive remodeling during both mammary gland development and breast cancer progression. A critical component of epithelial morphogenesis, apical-basal polarity in epithelial cells controls cell organization, proliferation, survival, and migration. This paper explores the evolving knowledge of apical-basal polarity programs' applications in breast tissue development and tumorigenesis. Cell lines, organoids, and in vivo models provide various approaches for studying apical-basal polarity in breast development and disease. We assess their individual strengths and limitations. ML 210 mw Furthermore, we illustrate how core polarity proteins influence branching morphogenesis and lactation development. Modifications to core polarity genes within breast cancer are analyzed, evaluating their associations with patient clinical outcomes. An analysis of the impact of increased or decreased levels of key polarity proteins on breast cancer's fundamental aspects: initiation, growth, invasion, metastasis, and resistance to treatment, is detailed here. We introduce studies here that show how polarity programs affect the regulation of the stroma, achieving this either by means of communication between epithelial and stromal cells, or via the signaling of polarity proteins in non-epithelial cells. The fundamental principle is that the role of individual polarity proteins is context-specific, modulated by the developmental stage, the cancer stage, and the cancer subtype.
The coordinated regulation of cell growth and patterning is necessary for the successful development of tissues. This analysis focuses on the evolutionarily maintained cadherins, Fat and Dachsous, and their impact on mammalian tissue development and disease. In Drosophila, the Hippo pathway and planar cell polarity (PCP) are regulated by Fat and Dachsous, controlling tissue growth. The Drosophila wing serves as a valuable model for studying how mutations in cadherins influence tissue development. Within mammalian tissues, multiple Fat and Dachsous cadherins are prevalent, while mutations in these cadherins that affect growth and tissue architecture are subject to the context. This investigation explores the impact of Fat and Dachsous gene mutations on mammalian development and their role in human diseases.
Immune cells are vital for the processes of pathogen recognition, elimination, and alerting other cells about potential threats. Immune response efficiency relies on the cells' motility in searching for pathogens, their interaction with other immune cells, and their diversification through asymmetrical cell division. ML 210 mw Cellular actions, governed by polarity, control motility, a key function for peripheral tissue scanning, pathogen detection, and immune cell recruitment to infection sites. Immune cell communication, particularly among lymphocytes, occurs via direct contact, the immunological synapse, inducing global cellular polarization and triggering lymphocyte activation. Finally, precursor immune cells divide asymmetrically, producing diverse daughter cell phenotypes, including memory and effector cells. This review integrates biological and physical approaches to investigate the impact of cellular polarity on the fundamental functions of immune cells.
Embryonic cells' initial adoption of unique lineage identities, the first cell fate decision, signifies the beginning of the developmental patterning. The differentiation of the embryonic inner cell mass (which becomes the organism) and the extra-embryonic trophectoderm (becoming the placenta) in mammals, particularly in mice, is frequently explained by the presence and impact of apical-basal polarity. Polarity development in the mouse embryo takes place by the eight-cell stage, marked by cap-like protein domains on the apical surface of each cell. Those cells that maintain this polarity during subsequent divisions constitute the trophectoderm, the rest becoming the inner cell mass. Research recently undertaken has led to significant progress in our knowledge of this process; this review will detail the underlying mechanisms of apical domain distribution and polarity establishment, assess factors influencing the very first cell fate decisions, considering cellular variations in the early embryo, and analyze the conservation of developmental mechanisms among diverse species, including humans.