A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis

Biological tubes possessing a curvilinear form and a hollow interior exist in most multicellular eukaryotes. In Eumetazoa, the tubes usually comprise an eminently complex network and enable the transport and exchange of fluids and gases between tissues and organs, but also between organisms and thei...

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Main Author: Wang, Shuoshuo
Other Authors: Prof. Dr. Achim Paululat
Format: Doctoral Thesis
Language:English
Published: 2012
Subjects:
Arf
Online Access:https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2012091110306
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spelling ndltd-uni-osnabrueck.de-oai-repositorium.ub.uni-osnabrueck.de-urn-nbn-de-gbv-700-20120911103062020-10-28T17:23:10Z A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis Wang, Shuoshuo Prof. Dr. Achim Paululat Prof. Dr. Christian Ungermann development tube formation Arf-GEF Gartenzwerg Garz Drosophila CG8487 tubulogenesis Arf genetic screen 42.23 - Entwicklungsbiologie 42.15 - Zellbiologie 42.20 - Genetik ddc:570 Biological tubes possessing a curvilinear form and a hollow interior exist in most multicellular eukaryotes. In Eumetazoa, the tubes usually comprise an eminently complex network and enable the transport and exchange of fluids and gases between tissues and organs, but also between organisms and their environment. Thus, tubular structures are both morphologically and physiologically integral parts of the animals. Based on a genetic screen for novel factors involved in heart tube differentiation and morphogenesis in Drosophila, the identified mutants were subdivided into several classes: cardiac hyperplasia (kuz and mam, both involved in the Notch-dependent cardiomyocyte specification, Publication 1); impaired cytokinesis (pav and tum, both components of the centralspindlin complex); a single ptc mutant showing a “truncated” heart (Publication 2); and a single loss-of-function mutant displaying reduced lumen diameter in epithelial tubes and perturbed secretion of ECM-components. The latter allele was mapped to the gene locus gartenzwerg (garz) that encodes a large ArfGEF. Due to its novelty, garz was selected as a central part of the thesis (Publication 3). Although garz seems to be expressed ubiquitously, its transcripts are abundant in active secreting cells of tubular structures. Moreover, mutations of garz abolish Golgi-integrity, cause massive retention of secretory cargo in the ER and arrest the apical transport of lipids and ECM molecules. As a consequence, lumen of the salivary glands and trachea fail to expand and show a decreased diameter. The observed phenotypes in tracheal network and salivary glands phenocopy those of COPI/COPII-subunits as well as actin-dependent secretion mutants, suggesting the underlying mechanism might be common. Thus, it is supposed that proper tubulogenesis needs Garz for initiation of the Arf1-COPI machinery. Furthermore, Golgi-based post-translational modifications, targeted sorting of vesicles, outward transport of proteins, or directed membrane delivery all depend on the secretory pathway, and such processes are essential in establishing polarized cells which build the tubular structures. In conclusion, this mechanism seems to be neither restricted to tubulogenesis nor specific to Drosophila. Due to the presence of garz homologues in every eukaryotic genomes, the Arf1/COPI based secretory pathway may play a universal role in metazoan development. 2012-09-11 doc-type:doctoralThesis https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2012091110306 eng http://rightsstatements.org/vocab/InC/1.0/ application/pdf application/zip
collection NDLTD
language English
format Doctoral Thesis
sources NDLTD
topic development
tube formation
Arf-GEF
Gartenzwerg
Garz
Drosophila
CG8487
tubulogenesis
Arf
genetic screen
42.23 - Entwicklungsbiologie
42.15 - Zellbiologie
42.20 - Genetik
ddc:570
spellingShingle development
tube formation
Arf-GEF
Gartenzwerg
Garz
Drosophila
CG8487
tubulogenesis
Arf
genetic screen
42.23 - Entwicklungsbiologie
42.15 - Zellbiologie
42.20 - Genetik
ddc:570
Wang, Shuoshuo
A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
description Biological tubes possessing a curvilinear form and a hollow interior exist in most multicellular eukaryotes. In Eumetazoa, the tubes usually comprise an eminently complex network and enable the transport and exchange of fluids and gases between tissues and organs, but also between organisms and their environment. Thus, tubular structures are both morphologically and physiologically integral parts of the animals. Based on a genetic screen for novel factors involved in heart tube differentiation and morphogenesis in Drosophila, the identified mutants were subdivided into several classes: cardiac hyperplasia (kuz and mam, both involved in the Notch-dependent cardiomyocyte specification, Publication 1); impaired cytokinesis (pav and tum, both components of the centralspindlin complex); a single ptc mutant showing a “truncated” heart (Publication 2); and a single loss-of-function mutant displaying reduced lumen diameter in epithelial tubes and perturbed secretion of ECM-components. The latter allele was mapped to the gene locus gartenzwerg (garz) that encodes a large ArfGEF. Due to its novelty, garz was selected as a central part of the thesis (Publication 3). Although garz seems to be expressed ubiquitously, its transcripts are abundant in active secreting cells of tubular structures. Moreover, mutations of garz abolish Golgi-integrity, cause massive retention of secretory cargo in the ER and arrest the apical transport of lipids and ECM molecules. As a consequence, lumen of the salivary glands and trachea fail to expand and show a decreased diameter. The observed phenotypes in tracheal network and salivary glands phenocopy those of COPI/COPII-subunits as well as actin-dependent secretion mutants, suggesting the underlying mechanism might be common. Thus, it is supposed that proper tubulogenesis needs Garz for initiation of the Arf1-COPI machinery. Furthermore, Golgi-based post-translational modifications, targeted sorting of vesicles, outward transport of proteins, or directed membrane delivery all depend on the secretory pathway, and such processes are essential in establishing polarized cells which build the tubular structures. In conclusion, this mechanism seems to be neither restricted to tubulogenesis nor specific to Drosophila. Due to the presence of garz homologues in every eukaryotic genomes, the Arf1/COPI based secretory pathway may play a universal role in metazoan development.
author2 Prof. Dr. Achim Paululat
author_facet Prof. Dr. Achim Paululat
Wang, Shuoshuo
author Wang, Shuoshuo
author_sort Wang, Shuoshuo
title A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
title_short A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
title_full A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
title_fullStr A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
title_full_unstemmed A genetic screen in Drosophila reveals the roles of ArfGEF Gartenzwerg in tube morphogenesis
title_sort genetic screen in drosophila reveals the roles of arfgef gartenzwerg in tube morphogenesis
publishDate 2012
url https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2012091110306
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AT wangshuoshuo geneticscreenindrosophilarevealstherolesofarfgefgartenzwergintubemorphogenesis
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