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Sequential Pulses of Apical Epithelial Secretion and Endocytosis Drive Airway Maturation in Drosophila
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.ORCID-id: 0000-0002-2933-1351
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut. (Christos Samakovlis)
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
Visa övriga samt affilieringar
2007 (Engelska)Ingår i: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 13, nr 2, s. 214-225Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The development of air-filled respiratory organs is crucial for survival at birth. We used a combination of live imaging and genetic analysis to dissect respiratory organ maturation in the embryonic Drosophila trachea. We found that tracheal tube maturation entails three precise epithelial transitions. Initially, a secretion burst deposits proteins into the lumen. Solid luminal material is then rapidly cleared from the tubes, and shortly thereafter liquid is removed. To elucidate the cellular mechanisms behind these transitions, we identified gas-filling-deficient mutants showing narrow or protein-clogged tubes. These mutations either disrupt endoplasmatic reticulum-to-Golgi vesicle transport or endocytosis. First, Sar1 is required for protein secretion, luminal matrix assembly, and diametric tube expansion. Subsequently, a sharp pulse of Rab5-dependent endocytic activity rapidly internalizes and clears luminal contents. The coordination of luminal matrix secretion and endocytosis may be a general mechanism in tubular organ morphogenesis and maturation.

Ort, förlag, år, upplaga, sidor
2007. Vol. 13, nr 2, s. 214-225
Nationell ämneskategori
Utvecklingsbiologi
Forskningsämne
utvecklingsbiologi
Identifikatorer
URN: urn:nbn:se:su:diva-32568DOI: 10.1016/j.devcel.2007.06.008ISI: 000248664300009OAI: oai:DiVA.org:su-32568DiVA, id: diva2:280972
Tillgänglig från: 2009-12-14 Skapad: 2009-12-14 Senast uppdaterad: 2022-02-25Bibliografiskt granskad
Ingår i avhandling
1. New roles for apical secretion and extracellular matrix assembly in Drosophila epithelial morphogenesis
Öppna denna publikation i ny flik eller fönster >>New roles for apical secretion and extracellular matrix assembly in Drosophila epithelial morphogenesis
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Branched tubular organs, such as the lung and vascular system fulfill the respiratory needs of most animals. Optimal tissue function relies on the uniform sizes and shapes of the constituting branches in each organ. The Drosophila tracheal airways provide a recognized genetic model system for identification and characterization of tube size regulators. We found that the programmed secretion and assembly of the apical extracellular matrix (ECM) is required for the expansion of the trachea and salivary glands (SG) tubes. We have characterized Vermiform (Verm) and Serpentine (Serp), two chitin-binding proteins with predicted polysaccharide deacetylase domains (ChLDs). Verm and Serp mutants show overelongated tubes, suggesting that luminal ECM modification restricts tracheal tube elongation. The luminal deposition of ChLDs, but not other secreted components, depends on paracellular septate junction integrity (SJs) in the tracheal epithelium. Deletion of the deacetylase domain renders Serp-GFP intracellular, arguing that the deacetylase domain harbors uncharacterized secretion signals. To explore this possibility we transferred the deacetylase domain from Serp to Gasp, another tracheal luminal protein, which requires the Emp24 adaptor for ER exit. The Gasp-Deac-GFP chimera was normally secreted in emp24 mutants indicating that the deacetylase domain contains potential ER-exit signals. To identify such signals we characterized conserved sequence motifs in the Serp deacetylase domain. Mutations of the N-glycosylation sites gradually reduced Serp-GFP luminal deposition suggesting that increased glycosylation enhances apical Serp secretion. By contrast, substitutions in three conserved amino acid stretches completely blocked the ER-exit of Serp-GFP. The mutated proteins were N-glycosylated suggesting that the motifs may be involved in a subsequent protein-folding step or facilitate ER exit through interactions with unidentified specific adaptors.

Ort, förlag, år, upplaga, sidor
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. s. 64
Nationell ämneskategori
Utvecklingsbiologi
Forskningsämne
utvecklingsbiologi
Identifikatorer
urn:nbn:se:su:diva-32564 (URN)978-91-7155-952-4 (ISBN)
Disputation
2010-01-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (Engelska)
Opponent
Handledare
Anmärkning
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript. Tillgänglig från: 2010-01-07 Skapad: 2009-12-14 Senast uppdaterad: 2022-02-25Bibliografiskt granskad
2. Airway maturation in Drosophila
Öppna denna publikation i ny flik eller fönster >>Airway maturation in Drosophila
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Tubes are a fundamental unit of organ design. Most of our major organs like the lung, kidney and vasculature are composed primarily of tubes. To identify fundamental biological principles of tubular organ formation we used the respiratory organ of Drosophila melanogaster, the trachea.This work dissects embryonic trachea maturation. Three precise epithelial transitions occur during airway maturation. A secretion burst deposits proteins into the lumen; then luminal material is cleared and finally liquid is removed. We identified the cellular mechanisms behind these transitions. Sar1 and γCOP are required for protein secretion, matrix assembly and tube expansion. Rab5-dependent endocytic activity internalizes and clears luminal contents. The data show how programmed transitions in cellular activities form functional airways, and may reflect a general mechanism in respiratory organ morphogenesis.We further focused on tube size regulation. We identified Melanotransferrin, a new component of septate junctions that limits tracheal tube elongation. MTf is a lipid- modified, iron-binding protein attached to epithelial cell membranes, similarly to its human homologue. We show that septate junction assembly during epithelial maturation relies on endocytosis and apicolateral recycling of iron-bound MTf. Mouse MTf complements the defects of Drosophila MTf mutants. This provides the first genetic model for the functional dissection of MTf in epithelial morphogenesis. In the last part, we describe two genes, which are selectively involved in tube diameter expansion. Obst-A and Gasp are closely related proteins with characteristic chitin-binding domains. They are strongly expressed in the trachea at the time of lumen expansion. The single and double mutants cause a tube diameter reduction, whereas their overexpression leads to its increase. We propose that Obst-A and Gasp organize luminal matrix assembly and thereby regulate the extent of tube diameter expansion.

Ort, förlag, år, upplaga, sidor
Stockholm: The Wenner-Gren Institute, Stockholm University, 2011. s. 18
Nationell ämneskategori
Utvecklingsbiologi
Forskningsämne
utvecklingsbiologi
Identifikatorer
urn:nbn:se:su:diva-62419 (URN)978-91-7447-338-4. (ISBN)
Disputation
2011-10-21, Högbomsalen, Geovetenskapens hus, Svante Arrhenius väg 12, 10:00 (Engelska)
Opponent
Handledare
Anmärkning
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.Tillgänglig från: 2011-09-29 Skapad: 2011-09-19 Senast uppdaterad: 2022-02-24Bibliografiskt granskad

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Tsarouhas, VasiliosSenti, Kirsten-AndréJayaram, Satish ArcotTiklová, KatarinaAdler, JeremySamakovlis, Christos

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Tsarouhas, VasiliosSenti, Kirsten-AndréJayaram, Satish ArcotTiklová, KatarinaAdler, JeremySamakovlis, Christos
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Wenner-Grens institut
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Developmental Cell
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