Analysis of the role of Nidogen/entactin in basement membrane assembly and morphogenesis in Drosophila

Jianli Dai, Beatriz Estrada, Sofie Jacobs, Besaiz Sánchez-Sánchez, Jia Tang, Mengqi Ma, Patricia Magadan, José C. Pastor-Pareja, Maria Dolores Martin-Bermudo

Preprint posted on 13 June 2018

Article now published in PLOS Genetics at

Necessary, or unnecessary, that is the question: Nidogen is not essential for overall Drosophila morphogenesis and viability, but required for proper basement membrane assembly in certain tissues.

Selected by Nargess Khalilgharibi

Categories: developmental biology

Context and background:

Basement membrane (BM) is a specific form of the extracellular matrix lining the basal side of the epithelial and endothelial tissues. The main BM constituents (i.e. laminin, collagen IV, perlecan and nidogen) have been conserved across evolution. The proper composition and structure of basement membrane is essential for correct tissue growth, organisation, differentiation and maintenance. Different BM components play distinct roles in its assembly and maintenance: it has been shown that laminin is required for incorporation of collagen IV into the BM, which will then help determine tissue shape, first by imposing a mechanical constriction on the cells and second through recruitment of perlecan that counters the constrictive effect of collagen IV1. However, the role of nidogen in BM assembly and maintenance is still not well understood. Indeed, in vitro studies propose that nidogen acts as a linker between laminin and collagen IV networks, thus playing a key role in BM assembly. On the other hand,  in vivo experiments have shown that loss of the only nidogen gene in C. elegans2 or either of the two nidogen genes in mice3, 4 does not affect BM assembly, organogenesis or survival, while simultaneous loss of the two genes in mice have shown to be lethal due to tissue-specific BM defects5. The authors of this preprint have investigated the role of nidogen in BM assembly of different tissues, using Drosophila as a model system.

Key findings:

Invertebrates, including Drosophila have only one nidogen gene. Developing a new anti-nidogen antibody, Dai et al. show that nidogen is found in the BM of most embryonic, larval and adult tissues. Interestingly, they also show that depending on the type of embryonic tissue, nidogen is assembled in different patterns. For example, while nidogen is present in continuous linear structures around muscles, gut and the ventral nerve cord (VNC), it has a dotted pattern along the visceral mesoderm (Fig. I). The authors identify fat body and blood cells as the main sources of nidogen, although some tissues (e.g. VNC) could produce their own nidogen.

To ask whether nidogen is required for animal morphogenesis, Dai et al. create a series of nidogen mutant lines using CRISPR/Cas9 technology. Nidogen elimination does not have an effect on viability and overall organogenesis, but leads to reduced fertility, similar to previous observations in C. elegans and in contrast to nidogen double-knockout mice. This suggests that some functions of nidogen might be specific to vertebrates. Next, the authors look for tissue-specific defects due to nidogen loss. They find that although nidogen loss does not affect BM in most tissues, it leads to lack of integrity in the BM of the larval fat body and adult flight muscles (Fig II). In addition, laminin and collagen IV networks appear uncoupled in the fat body BM of nidogen mutants, in agreement with in vitro studies suggesting a role of nidogen as a linker between these networks. This was further confirmed by a detailed functional analysis of the different nidogen domains.

Finally, the authors investigate the dependency of nidogen incorporation into the BM on the other BM components. They find that the nidogen assembly requirements are tissue-specific: while only laminin is required for nidogen incorporation into the BM of embryonic gut, muscle and VNC tissues, both laminin and collagen IV are required for nidogen assembly in larval fat body.


Figure adapted from Dai et al. (I) Confocal images of embryonic tissues stained with anti-Ndg antibody. Images show gut and VNC (top arrow and arrowhead) and visceral mesoderm (bottom). (II) Laminin and collagen IV networks on the larval fat body surface in wild type (top) and nidogen mutant (bottom) flies. The BM becomes fractured due to nidogen loss.


Why I chose this preprint:

Nidogen is one of the four main BM components, whose role in BM formation and maintenance is not well known. This is partly due to seemingly contradictory observations from various in vitro and in vivo studies. Looking at different tissues during Drosophila development, Dai et al.  show that nidogen structure, assembly and function is tissue-specific, which could explain its vitality for development of some tissues, and its dispensability for some others.

Questions for the authors:

This preprint shows that nidogen assembly and function is tissue-specific. It would be interesting to investigate why loss of nidogen affects larval fat body but not many other tissues. This preprint shows that the nidogen organisation is also tissue-specific. Could this organisational difference (e.g. continuous mesh-like structure in the fat body versus dotted pattern in visceral mesoderm) explain the effects of its loss in some tissues, but not others? It would also be interesting to investigate whether nidogen acts as a linker in tissues other than the fat body.


  1. Pastor-Pareja, José C. & Xu, T. Shaping Cells and Organs in Drosophila by Opposing Roles of Fat Body-Secreted Collagen IV and Perlecan. Developmental Cell 21, 245-256 (2011).
  2. Kang, S.H. & Kramer, J.M. Nidogen Is Nonessential and Not Required for Normal Type IV Collagen Localization in Caenorhabditis elegans. Molecular Biology of the Cell 11, 3911-3923 (2000).
  3. Murshed, M. et al. The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation. Molecular and Cellular Biology 20, 7007-7012 (2000).
  4. Schymeinsky, J. et al. Gene Structure and Functional Analysis of the Mouse Nidogen-2 Gene: Nidogen-2 Is Not Essential for Basement Membrane Formation in Mice. Molecular and Cellular Biology 22, 6820-6830 (2002).
  5. Bader, B.L. et al. Compound Genetic Ablation of Nidogen 1 and 2 Causes Basement Membrane Defects and Perinatal Lethality in Mice. Molecular and Cellular Biology 25, 6846-6856 (2005).

Tags: basement membrane, drosophila, ecm, epithelia, extracellular matrix, fruit fly

Posted on: 30 August 2018 , updated on: 31 August 2018


Read preprint (No Ratings Yet)

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the developmental biology category:

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)


List by Nándor Lipták


The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!


List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020


List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.


List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020


List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020


List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.


List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.


List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.


List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.


List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.


List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London


List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.


List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019


List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.


List by Shikha Nayar