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Control of tube diameter expansion by secreted chitin-binding proteins
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Developmental Biology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Developmental Biology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The size and shape of epithelial tubes determine the transporting capacities of tubular organs. Here, we analyze two genes involved in airway tube size regulation in Drosophila. Obst-A and gasp encode secreted proteins with chitin binding domains that are conserved among insect species. mRNA in situ hybridizations show that both genes are strongly expressed during airway tube expansion. Gasp protein is secreted into the airway tubes and colocalizes with a chitin binding probe and other chitin binding proteins. Analysis of obst-A and gasp single mutants and obst-A; gasp double mutant shows that both genes are required for larval elongation and airway tube dilation. The assembly of the apical chitinous matrix of the airway tubes is defective in gasp and Obst-A mutants. The defects become exaggerated in double mutants indicating that the genes have partially redundant functions in chitin structure modification. The phenotypes in luminal chitin assembly in the airway tubes are accompanied with a corresponding reduction of tube diameter in the mutants. Conversely, overexpression of Obst-A or Gasp in the airways expands the tube circumference.  Our results indicate that the level of distinct matrix binding proteins in the tubes determines the extent of diametric growth. We propose that Obst-A and Gasp organize the assembly of the luminal matrix and thereby provide distending forces that stretch the apical cell membranes to expand tube diameter accordingly.

National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-62417OAI: oai:DiVA.org:su-62417DiVA: diva2:441690
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2011-09-29Bibliographically approved
In thesis
1. Airway maturation in Drosophila
Open this publication in new window or tab >>Airway maturation in Drosophila
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2011. 18 p.
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-62419 (URN)978-91-7447-338-4. (ISBN)
Public defence
2011-10-21, Högbomsalen, Geovetenskapens hus, Svante Arrhenius väg 12, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.Available from: 2011-09-29 Created: 2011-09-19 Last updated: 2011-09-29Bibliographically approved

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