scholarly journals Regulators of the secretory pathway have distinct inputs into single-celled branching morphogenesis and seamless tube formation in the Drosophila trachea

2021 ◽  
Author(s):  
Christopher M Bourne ◽  
Daniel C Lai ◽  
Jodi Schottenfeld-Roames
Keyword(s):  
Secretory Pathway ◽  
Apical Membrane ◽  
Branching Morphogenesis ◽  
Terminal Cell ◽  
Seamless Tube ◽  
Cell Morphogenesis ◽  
Tracheal System ◽  
Organ Systems ◽  
Epithelial Junctions ◽  
Membrane Growth

Biological tubes serve as conduits through which gas, nutrients and other important fluids are delivered to tissues. Most biological tubes consist of multiple cells connected by epithelial junctions. Unlike these multicellular tubes, seamless tubes are unicellular and lack junctions. Seamless tubes are present in various organ systems, including the vertebrate vasculature, C.elegans excretory system, and Drosophila tracheal system. The Drosophila tracheal system is a network of air-filled tubes that delivers oxygen to all tissues. Specialized cells within the tracheal system, called terminal cells, branch extensively and form seamless tubes. Terminal tracheal tubes are polarized; the lumenal membrane has apical identity whereas the outer membrane exhibits basal characteristics. Although various aspects of membrane trafficking have been implicated in terminal cell morphogenesis, the precise secretory pathway requirements for basal and apical membrane growth have yet to be elucidated. In the present study, we demonstrate that anterograde trafficking, retrograde trafficking and Golgi-to-plasma membrane vesicle fusion are each required for the complex branched architecture of the terminal cell, but their inputs during seamless lumen formation are more varied. The COPII subunit, Sec 31, and ER exit site protein, Sec16, are critical for subcellular tube architecture, whereas the SNARE proteins Syntaxin 5, Syntaxin 1 and Syntaxin15 are required for seamless tube growth and maintenance. These data suggest that distinct components of the secretory pathway have differential contributions to basal and apical membrane growth and maintenance during terminal cell morphogenesis.

Cellular and molecular mechanisms involved in branching morphogenesis of the Drosophila tracheal system

2004 ◽  
Vol 97 (6) ◽  
pp. 2347-2353 ◽  
Author(s):  
Clemens Cabernard ◽  
Marc Neumann ◽  
Markus Affolter
Keyword(s):  
Lung Development ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Genetic Network ◽  
Branching Morphogenesis ◽  
Model Systems ◽  
Tracheal System ◽  
Organ Systems ◽  
Invertebrate Model ◽  
Complex Organ

Recent comparative studies have shown that, in many instances, the genetic network underlying the development of distinct organ systems is similar in invertebrate and vertebrate organisms. Genetically well-characterized, simple invertebrate model systems, such as Caenorhabditis elegans and Drosophila melanogaster, can thus provide useful insight for understanding more complex organ systems in vertebrates. Here, we summarize recent progress in the genetic analysis of tracheal development in Drosophila and compare the results to studies aimed at a better understanding of lung development in mouse and man. Clearly, both striking similarities and important differences are apparent, but it might still be too early to conclude whether the former or the latter prevail.

scholarly journals Ca2+-ATPase protein expression in mammary tissue

2000 ◽  
Vol 279 (5) ◽  
pp. C1595-C1602 ◽  
Author(s):  
Timothy A. Reinhardt ◽  
Adelaida G. Filoteo ◽  
John T. Penniston ◽  
Ronald L. Horst
Keyword(s):  
Protein Expression ◽  
Milk Fat ◽  
Secretory Pathway ◽  
Apical Membrane ◽  
Mammary Tissue ◽  
Splice Form ◽  
Rt Pcr ◽  
Milk Fat Globule ◽  
Alternatively Spliced ◽  
Fat Globule

Protein expression of plasma membrane Ca2+-ATPases (PMCAs) and the putative Golgi secretory pathway Ca2+-ATPase (SPCA) was examined in rat mammary tissue. As lactation started, PMCA protein expression increased dramatically, and this increased expression paralleled milk production. Mammary PMCA was primarily PMCA2b but was ∼4,000 daltons larger than expected. RT-PCR showed that the primary mammary PMCA2b transcript was alternatively spliced, at splice site A, to include an additional 135 bp, resulting in the insertion of 45 amino acids. This splice form is designated 2bw. PMCA2bw is secreted into milk, associated with the milk fat globule membrane. Therefore, PMCA2bw is located on the apical membrane of the secretory cell. Smaller amounts of PMCA1b and 4b protein were found in mammary tissue. PMCA4b was the major PMCA expressed in developing tissue, and its level declined as lactation started. PMCA1b expression increased moderately during lactation. SPCA protein expression increased 1 wk before parturition and increased further as lactation proceeded. The abundance and cell location of PMCA2b suggest that it is important for macro-Ca2+ homeostasis in lactating tissue. The pattern of expression and abundance of SPCA suggest that it is a candidate for the Golgi Ca2+-ATPase.

Gene Trap, Gene Knockout, Gene Knock-In, and Transgenics in Vascular Development

1999 ◽  
Vol 82 (08) ◽  
pp. 865-869 ◽  
Author(s):  
Thomas Sato
Keyword(s):  
Animal Models ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
System Development ◽  
Gene Knockout ◽  
Vascular Development ◽  
Branching Morphogenesis ◽  
Abnormal Development ◽  
Organ Systems ◽  
Almost All

IntroductionThe vascular system is one of the first organ systems to develop in our bodies. Normal development and maturation of the physiological functions of almost all of the other organs are critically dependent on the accurate and tightly controlled establishment of the vascular system. Our understanding of the mechanisms underlying the formation of the vascular system during development is still in its infancy. With further understanding of these mechanisms, we may eventually be able to correct the abnormal development and the malfunctioning of many organs by therapeutically modulating the morphology and/or physiological function of the vascular system.Our further understanding of the vascular development can, in part, be achieved by discovering the molecules that play critical roles in this process. We could also achieve this goal by learning more about the functions of previously identified molecules in the vascular system. Discovery of new processes underlying the development of the vascular system will also contribute to further understanding of these molecular mechanisms.Recent advances, using the whole genome approach, have resulted in a flood of new information. This trend will continue, and fortunately, a number of molecular reagents will become available. Therefore, the field will likely experience an exponential growth in terms of novel biological insights and discovering the mechanisms of vascular system development.Occasionally, reductionistic approaches help to systematically address a number of biological problems, including the problems associated with vascular system development. One such approach is to choose an organism that allows us to systematically address these biological questions. The choice of animal models that are well-suited for the study of a particular question has led to a large number of discoveries. To address questions in vascular system development, current research has focused on animal models, including fish, frog, bird, and mouse, and also studies involving humans. It is also worthwhile to note that the branching morphogenesis of the fly trachea system has been utilized to address fundamental questions of vascular morphogenesis.This chapter will summarize the genomic manipulation of the murine vascular system to address questions regarding vascular development. In addition, the advances that have been made in this field using such methods will be summarized.

scholarly journals Septins Coordinate with Microtubules and Actin to Initiate Cell Morphogenesis

2019 ◽  
Author(s):  
Diana Bogorodskaya ◽  
Lee A. Ligon
Keyword(s):  
Branching Morphogenesis ◽  
Response To Treatment ◽  
Cell Morphogenesis ◽  
Microtubule Organization ◽  
Basal Surface ◽  
Linear Rate ◽  
Epithelial Sheet ◽  
District Role ◽  
Hepatocyte Growth ◽  
Cytoskeletal System

AbstractMany organs are formed by a process of branching morphogenesis, which begins with the formation of cytoplasmic extensions from the basal surface of polarized cells in an epithelial sheet. To study this process, we used a system of polarized epithelial spheroids, which emit cytoplasmic extensions in response to treatment with hepatocyte growth factor. We found that these extensions contain both actin and microtubules, but also septins, which are localized to microtubule bundles and appear to be important in maintaining microtubule organization. We found that these extensions are highly dynamic and form at a non-linear rate. We also demonstrated that the coordinated activity of microtubules, actin, and septins is necessary for the formation and dynamic behavior of extensions. Each cytoskeletal system plays a district role in this process, with microtubules enabling persistent growth of the extensions, actin enabling extension dynamics, and septins organizing microtubules in the extensions and supporting the extension formation. Together, our data offer insights into the dynamics of early morphogenic extensions and the distinct, but coordinated, roles of cytoskeleton in early morphogenesis.

scholarly journals (Pro)renin receptor regulates lung development via the Wnt/β-catenin signaling pathway

2019 ◽  
Vol 317 (2) ◽  
pp. L202-L211 ◽  
Author(s):  
Jie Liu ◽  
Yafan Zhou ◽  
Yalan Liu ◽  
Lei Li ◽  
Yan Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Development ◽  
Temporal Distribution ◽  
Renin Angiotensin System ◽  
Bronchial Epithelium ◽  
Branching Morphogenesis ◽  
Lung Hypoplasia ◽  
Tunel Staining ◽  
Organ Systems ◽  
Proliferation And Apoptosis

The (pro)renin receptor [(P)RR] binds to prorenin to activate the renin-angiotensin system and is essential for the development of many different organ systems. Whether the (P)RR also plays a role in lung development is unknown. Immunostaining was used to determine the spatial-temporal distribution of (P)RR in the embryonic, postnatal, and adult lungs. We created a lung-specific (P)RR knockout mouse [ Foxd1cre/+ -(P)RRflox/flox] and assessed changes in lung morphology, cell proliferation, and apoptosis using immunohistochemistry and TUNEL staining. (P)RR function was confirmed by using siRNA to knock down (P)RR in human bronchial epithelial cells (HBECs) and then using the CCK-8 assay and flow cytometry to assess cell proliferation and apoptosis. Gene expression changes after knockdown were assessed by RT-PCR and Western blotting. (P)RR is expressed in the club cells of the bronchial epithelium, and expression increases throughout development. Lung-specific (P)RR knockout disrupted branching morphogenesis, leading to lung hypoplasia and neonatal mortality. These defects were associated with increased apoptosis and decreased proliferation of the pulmonary epithelial and mesenchymal cells and may be mediated by downregulation of Wnt11, β-catenin, and Axin2. (P)RR regulates lung development through canonical Wnt/β-catenin signaling and may present a new target for strategies to treat lung hypoplasia.

scholarly journals The Cytoplasmic Tail of Rhodopsin Acts as a Novel Apical Sorting Signal in Polarized MDCK Cells

1998 ◽  
Vol 142 (5) ◽  
pp. 1245-1256 ◽  
Author(s):  
Jen-Zen Chuang ◽  
Ching-Hwa Sung
Keyword(s):  
Secretory Pathway ◽  
Apical Membrane ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Brefeldin A ◽  
Cytoplasmic Tail ◽  
Apical Plasma Membrane ◽  
Glutathione S Transferase ◽  
Sorting Signals ◽  
Apical Sorting

All basolateral sorting signals described to date reside in the cytoplasmic domain of proteins, whereas apical targeting motifs have been found to be lumenal. In this report, we demonstrate that wild-type rhodopsin is targeted to the apical plasma membrane via the TGN upon expression in polarized epithelial MDCK cells. Truncated rhodopsin with a deletion of 32 COOH-terminal residues shows a nonpolar steady-state distribution. Addition of the COOH-terminal 39 residues of rhodopsin redirects the basolateral membrane protein CD7 to the apical membrane. Fusion of rhodopsin's cytoplasmic tail to a cytosolic protein glutathione S-transferase (GST) also targets this fusion protein (GST–Rho39Tr) to the apical membrane. The targeting of GST–Rho39Tr requires both the terminal 39 amino acids and the palmitoylation membrane anchor signal provided by the rhodopsin sequence. The apical transport of GST–Rho39Tr can be reversibly blocked at the Golgi complex by low temperature and can be altered by brefeldin A treatment. This indicates that the membrane-associated GST–Rho39Tr protein may be sorted along a yet unidentified pathway that is similar to the secretory pathway in polarized MDCK cells. We conclude that the COOH-terminal tail of rhodopsin contains a novel cytoplasmic apical sorting determinant. This finding further indicates that cytoplasmic sorting machinery may exist in MDCK cells for some apically targeted proteins, analogous to that described for basolaterally targeted proteins.

scholarly journals Retinoic Acid: A Key Regulator of Lung Development

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 152 ◽  
Author(s):  
Hugo Fernandes-Silva ◽  
Henrique Araújo-Silva ◽  
Jorge Correia-Pinto ◽  
Rute S Moura
Keyword(s):  
Retinoic Acid ◽  
Lung Development ◽  
Target Genes ◽  
Branching Morphogenesis ◽  
Developmental Pathways ◽  
Adult Tissue ◽  
Spatiotemporal Regulation ◽  
Organ Systems ◽  
Developmental Phases ◽  
Pulmonary Vascular Development

Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During lung development, there is a spatiotemporal regulation of RA levels that assures the formation of a fully functional organ. RA signaling influences lung specification, branching morphogenesis, and alveolarization by regulating the expression of particular target genes. Moreover, cooperation with other developmental pathways is essential to shape lung organogenesis. This review focuses on the events regulated by retinoic acid during lung developmental phases and pulmonary vascular development; also, it aims to provide a snapshot of RA interplay with other well-known regulators of lung development.

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