Cargando…

Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly

Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents...

Descripción completa

Detalles Bibliográficos
Autores principales: Dai, Jianli, Estrada, Beatriz, Jacobs, Sofie, Sánchez-Sánchez, Besaiz J., Tang, Jia, Ma, Mengqi, Magadán-Corpas, Patricia, Pastor-Pareja, José C., Martín-Bermudo, María D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177204/
https://www.ncbi.nlm.nih.gov/pubmed/30260959
http://dx.doi.org/10.1371/journal.pgen.1007483
_version_ 1783361832100036608
author Dai, Jianli
Estrada, Beatriz
Jacobs, Sofie
Sánchez-Sánchez, Besaiz J.
Tang, Jia
Ma, Mengqi
Magadán-Corpas, Patricia
Pastor-Pareja, José C.
Martín-Bermudo, María D.
author_facet Dai, Jianli
Estrada, Beatriz
Jacobs, Sofie
Sánchez-Sánchez, Besaiz J.
Tang, Jia
Ma, Mengqi
Magadán-Corpas, Patricia
Pastor-Pareja, José C.
Martín-Bermudo, María D.
author_sort Dai, Jianli
collection PubMed
description Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents of BMs are two independent networks of Laminin and Type IV Collagen in addition to the proteoglycan Perlecan and the glycoprotein Nidogen/entactin (Ndg). The ability of Ndg to bind in vitro Collagen IV and Laminin, both with key functions during embryogenesis, anticipated an essential role for Ndg in morphogenesis linking the Laminin and Collagen IV networks. This was supported by results from cultured embryonic tissue experiments. However, the fact that elimination of Ndg in C. elegans and mice did not affect survival strongly questioned this proposed linking role. Here, we have isolated mutations in the only Ndg gene present in Drosophila. We find that while, similar to C.elegans and mice, Ndg is not essential for overall organogenesis or viability, it is required for appropriate fertility. We also find, alike in mice, tissue-specific requirements of Ndg for proper assembly and maintenance of certain BMs, namely those of the adipose tissue and flight muscles. In addition, we have performed a thorough functional analysis of the different Ndg domains in vivo. Our results support an essential requirement of the G3 domain for Ndg function and unravel a new key role for the Rod domain in regulating Ndg incorporation into BMs. Furthermore, uncoupling of the Laminin and Collagen IV networks is clearly observed in the larval adipose tissue in the absence of Ndg, indeed supporting a linking role. In light of our findings, we propose that BM assembly and/or maintenance is tissue-specific, which could explain the diverse requirements of a ubiquitous conserved BM component like Nidogen.
format Online
Article
Text
id pubmed-6177204
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-61772042018-10-19 Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly Dai, Jianli Estrada, Beatriz Jacobs, Sofie Sánchez-Sánchez, Besaiz J. Tang, Jia Ma, Mengqi Magadán-Corpas, Patricia Pastor-Pareja, José C. Martín-Bermudo, María D. PLoS Genet Research Article Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents of BMs are two independent networks of Laminin and Type IV Collagen in addition to the proteoglycan Perlecan and the glycoprotein Nidogen/entactin (Ndg). The ability of Ndg to bind in vitro Collagen IV and Laminin, both with key functions during embryogenesis, anticipated an essential role for Ndg in morphogenesis linking the Laminin and Collagen IV networks. This was supported by results from cultured embryonic tissue experiments. However, the fact that elimination of Ndg in C. elegans and mice did not affect survival strongly questioned this proposed linking role. Here, we have isolated mutations in the only Ndg gene present in Drosophila. We find that while, similar to C.elegans and mice, Ndg is not essential for overall organogenesis or viability, it is required for appropriate fertility. We also find, alike in mice, tissue-specific requirements of Ndg for proper assembly and maintenance of certain BMs, namely those of the adipose tissue and flight muscles. In addition, we have performed a thorough functional analysis of the different Ndg domains in vivo. Our results support an essential requirement of the G3 domain for Ndg function and unravel a new key role for the Rod domain in regulating Ndg incorporation into BMs. Furthermore, uncoupling of the Laminin and Collagen IV networks is clearly observed in the larval adipose tissue in the absence of Ndg, indeed supporting a linking role. In light of our findings, we propose that BM assembly and/or maintenance is tissue-specific, which could explain the diverse requirements of a ubiquitous conserved BM component like Nidogen. Public Library of Science 2018-09-27 /pmc/articles/PMC6177204/ /pubmed/30260959 http://dx.doi.org/10.1371/journal.pgen.1007483 Text en © 2018 Dai et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dai, Jianli
Estrada, Beatriz
Jacobs, Sofie
Sánchez-Sánchez, Besaiz J.
Tang, Jia
Ma, Mengqi
Magadán-Corpas, Patricia
Pastor-Pareja, José C.
Martín-Bermudo, María D.
Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title_full Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title_fullStr Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title_full_unstemmed Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title_short Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly
title_sort dissection of nidogen function in drosophila reveals tissue-specific mechanisms of basement membrane assembly
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177204/
https://www.ncbi.nlm.nih.gov/pubmed/30260959
http://dx.doi.org/10.1371/journal.pgen.1007483
work_keys_str_mv AT daijianli dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT estradabeatriz dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT jacobssofie dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT sanchezsanchezbesaizj dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT tangjia dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT mamengqi dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT magadancorpaspatricia dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT pastorparejajosec dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly
AT martinbermudomariad dissectionofnidogenfunctionindrosophilarevealstissuespecificmechanismsofbasementmembraneassembly