Embryonic geometry underlies phenotypic variation in decanalized conditions
Posted on: 6 May 2019
Preprint posted on 16 March 2019
Article now published in eLife at http://dx.doi.org/10.7554/eLife.47380
Gene regulatory networks provide robustness against variation in embryonic geometry
Selected by Sundar NaganathanCategories: biophysics, developmental biology
Brief background on Drosophila segmentation
Segmentation refers to serial repetition of similar anatomical modules along the body axis, which results in formation of the head, thorax and abdomen in insects. In Drosophila this segmental pattern is laid down during the first 3 hours of development through a complex hierarchical network of regulatory interactions. A maternally provided mix of different mRNAs that have spatially distinct expression patterns provide the initial regulatory inputs for segmentation. For example, Bicoid (Bcd) protein forms an anterior-to-posterior gradient and Nanos (nos) forms a posterior-to-anterior gradient in the embryo. These maternal gradients activate downstream target genes called gap genes in a concentration dependent manner. Gap genes (e.g. hunchback (hb), Krüppel (Kr), knirps (kni), giant (gt)) are expressed in broad, overlapping domains about 10-20 nuclei wide1. Gap genes regulate expression of pair-rule genes (e.g. hairy, eve, runt), which are the first genes to be expressed in spatially periodic patterns (7-8 stripes about 4 nuclei wide) in the Drosophila embryo2. Finally, at the onset of gastrulation, the segment-polarity genes turn on, which are spatially regulated by pair-rule genes. The segment-polarity genes (e.g. en, odd, slp) show expression in 14 narrow stripes (about 1 or 2-nuclei wide), which are ultimately involved in positioning the morphological segment boundaries later in development.
The question
Most species have abundant genetic variation and experience a range of environmental conditions and yet phenotypic variation is low. This ability of an organism to maintain a stable phenotype irrespective of genetic and environmental variability is termed as canalization. This concept, first developed by C. H. Waddington in 19423, has since been extensively explored mainly with respect to complex gene regulatory networks that have feed-forward and feedback loops, which ultimately provide robustness to the underlying biological processes.
In addition to genetic and environmental variability, are there other sources of variation that canalization works against to enable developmental robustness? To answer this question, Huang and Saunders chose the early Drosophila embryonic segmentation process and generated decanalized conditions to identify sources of variation that leads to inter-individual variability in phenotypes.
Key discovery
The authors used a previously generated bcd knockout (KO) mutant4, where the anterior embryonic cuticle patterning was entirely defective and the posterior patterning defects were more variable than wild type. This phenotypic variability is due to noisy gap gene expression patterns that emerge in the absence of a maternal Bcd gradient. Similar phenotypic variation was observed in embryos grown from a single pair of bcdKO parents suggesting that environmental conditions and genetic background contributes little to inter-individual variation in the conducted experiments. Interestingly, the variation in the number of segment polarity gene stripes in bcdKO embryos (performed for the gene engrailed, en) was highly correlated with embryonic length along the anterior-posterior (AP) axis and increased variation in gap gene expression patterns was observed with increasing embryonic length. This suggests that embryonic geometry could be a source of variation leading to inter-individual phenotypic variation.
Does a change in embryonic geometry alone alter embryonic pattern formation? To answer this, the authors targeted atypical cadherin Fat2 (fat2RNAi) in the follicle cells to generate embryos with significantly shortened embryonic length, though the total embryo volume only reduced by ~8%. These embryos hatched, with healthy larvae. Under these conditions, changes in gap gene expression patterns were observed with these changes correlating with embryonic length. This implied strongly that the segmentation network is highly robust to variations in embryonic geometry.
The authors then overexpressed bcd, a decanalized condition similar to the bcdKO condition, which also led to increased variability in En stripe patterns with decreased embryonic length. Similar phenotypes were also observed in the cuticle patterning. Interestingly, in embryos significantly shorter in AP length than wild type, the A4 cuticle segment was observed to be defective more frequently than other cuticle segments. Based on the expression profiles of the gap genes, the authors propose that the complex gene regulatory network is vulnerable at specific spatial locations in the embryo under decanalized conditions leading to defects in the A4 cuticle segment.
Why I chose this preprint
Embryogenesis is an intricately woven dance regulated spatiotemporally by complex gene regulatory processes. Decades of work on Drosophila early embryos have uncovered many of the hierarchical regulatory networks that pattern the segmented body plan. This volume of available data allows for investigating questions on robustness of gene regulatory networks and their evolution. By using this information, the work performed in this manuscript shows that gene regulatory networks have likely evolved to also provide robustness against varying embryonic geometry. Importantly, they also show that under decanalized conditions, e.g. when bcd is overexpressed, there are likely to be vulnerable points in the regulatory network leading to morphogenetic defects in precise spatial locations in the embryo.
Open questions
- Based on a qualitative description of gene expression profiles, the authors have predicted that there is likely to be a susceptible point in the gene regulatory network leading to biased phenotypes in the A4 cuticle segment. Given the volume of data available at the authors’ disposal, it will be wonderful to build or use previously published mathematical models to quantitatively predict this bias.
- The number of En stripes shows positive linear correlation with embryonic length in bcdKO embryos, whereas the number of stripes remains constant in fat2RNAi embryos. Does this mean that the number of stripes is scaled with embryonic length in bcdKO conditions, whereas the width of the stripes is scaled in fat2RNAi conditions ensuring constant number of stripes? What determines these different scaling processes?
- Significantly different changes in embryonic length have been achieved mainly through genetically altered conditions (bcdKO, fat2RNAi and bcd overexpression). In this scenario, it is not clear to me the authors’ claim of embryonic geometry as an “additional source of variation” that gene regulatory networks have to buffer against.
References
- Jaeger J., The gap gene network, Cell. Mol. Life Sci., 2011.
- Clark E., Dynamic patterning by the Drosophila pair- rule network reconciles long-germ and short- germ segmentation, PLoS Biol., 2017.
- Waddington C. H., Canalization of development and the inheritance of acquired characters, Nature, 1942.
- Huang A, et al., Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila embryo, eLife, 2017.
doi: https://doi.org/10.1242/prelights.10541
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the biophysics category:
Motor Clustering Enhances Kinesin-driven Vesicle Transport
Sharvari Pitke
Global coordination of protrusive forces in migrating immune cells
yohalie kalukula
Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane
Sristilekha Nath
Also in the developmental biology category:
Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis
Ankita Walvekar
Actin-based deformations of the nucleus control multiciliated ependymal cell differentiation
Ryan Harrison
HIF1A contributes to the survival of aneuploid and mosaic pre-implantation embryos
Anchel De Jaime Soguero
preListsbiophysics category:
in thepreLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
List by | preLights peer support |
66th Biophysical Society Annual Meeting, 2022
Preprints presented at the 66th BPS Annual Meeting, Feb 19 - 23, 2022 (The below list is not exhaustive and the preprints are listed in no particular order.)
List by | Soni Mohapatra |
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 |
Biophysical Society Meeting 2020
Some preprints presented at the Biophysical Society Meeting 2020 in San Diego, USA.
List by | Tessa Sinnige |
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. |
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 |
Biomolecular NMR
Preprints related to the application and development of biomolecular NMR spectroscopy
List by | Reid Alderson |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
List by | Joseph Jose Thottacherry |
Also in the developmental biology category:
BSDB/GenSoc Spring Meeting 2024
A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.
List by | Joyce Yu, Katherine Brown |
GfE/ DSDB meeting 2024
This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.
List by | Joyce Yu |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
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 |
Fibroblasts
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 |