Computer Science, Morphogenesis and Variability From developing code to decoding development

Research

We investigate how embryos reproducibly build complex organisms. Our core question: how to quantify developmental variability across spatio-temporal scales? We combine fluorescence microscopy, spatial transcriptomics, and machine learning to analyze morphogenesis at single-cell resolution in model organisms including Drosophila and ascidians.

Our two main axes are (1) building morphological and molecular atlases of embryogenesis through non-linear co-registration of multiple embryos, and (2) developing machine-learning algorithms to detect and quantify scales of reproducibility throughout development.

Highlighted

Contact area dependent cell communication and the morphological invariance of ascidian embryogenesis
Contact area–dependent cell communication and the morphological invariance of ascidian embryogenesis
Léo Guignard, Ulla-Maj Fiúza, Bruno Leggio, Julien Laussu, Emmanuel Faure, …, Kilian Biasuz, Lars Hufnagel, Grégoire Malandain, Christophe Godin, Patrick Lemaire
Science  ·  03 Jul 2020  ·  doi:10.1126/science.aar5663
ascidian morphogenesis cell-communication

All

2026

sc3D: A Comprehensive Tool for 3D Spatial Transcriptomic Analysis
sc3D: A Comprehensive Tool for 3D Spatial Transcriptomic Analysis
Miquel Sendra, Adriano Bolondi, Léo Guignard
BIO-PROTOCOL  ·  01 Jan 2026  ·  doi:10.21769/bioprotoc.5607

2025

Fast volumetric fluorescence lifetime imaging of multicellular systems using single-objective light-sheet microscopy
Fast volumetric fluorescence lifetime imaging of multicellular systems using single-objective light-sheet microscopy
Valentin Dunsing-Eichenauer, Johan Hummert, Claire Chardès, Thomas Schönau, Léo Guignard, …, Jean-Baptiste Sibarita, Virgile Viasnoff, Ivan Michel Antolovic, Rainer Erdmann, Pierre-François Lenne
Communications Biology  ·  29 Nov 2025  ·  doi:10.1038/s42003-025-09221-2
Longitudinal tracking of neuronal activity from the same cells in the developing brain using Track2p
Longitudinal tracking of neuronal activity from the same cells in the developing brain using Track2p
Jure Majnik, Manon Mantez, Sofia Zangila, Stéphane Bugeon, Leo Guignard, Jean-Claude Platel, Rosa Cossart
openRxiv  ·  01 Mar 2025  ·  doi:10.1101/2025.02.26.640367

2024

A quantitative pipeline for whole-mount deep imaging and analysis of multi-layered organoids across scales
A quantitative pipeline for whole-mount deep imaging and analysis of multi-layered organoids across scales
Alice Gros, Jules Vanaret, Valentin Dunsing-Eichenauer, Agathe Rostan, Philippe Roudot, Pierre-François Lenne, Léo Guignard, Sham Tlili
openRxiv  ·  14 Aug 2024  ·  doi:10.1101/2024.08.13.607832
organoids imaging
Epigenetic priming of embryonic lineages in the mammalian epiblast
Epigenetic priming of embryonic lineages in the mammalian epiblast
Miquel Sendra, Katie McDole, Daniel Jimenez-Carretero, Juan de Dios Hourcade, Susana Temiño, …, Léo Guignard, Philipp J Keller, Fátima Sánchez-Cabo, Jorge N. Domínguez, Miguel Torres
openRxiv  ·  11 Jan 2024  ·  doi:10.1101/2024.01.11.575188

2023

Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis
Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis
Abhishek Sampath Kumar, Luyi Tian, Adriano Bolondi, Amèlia Aragonés Hernández, Robert Stickels, …, Yechiel Elkabetz, Evan Z. Macosko, Léo Guignard, Fei Chen, Alexander Meissner
Nature Genetics  ·  13 Jul 2023  ·  doi:10.1038/s41588-023-01435-6
spatial-transcriptomics mouse-embryo

2022

Automated reconstruction of whole-embryo cell lineages by learning from sparse annotations
Automated reconstruction of whole-embryo cell lineages by learning from sparse annotations
Caroline Malin-Mayor, Peter Hirsch, Leo Guignard, Katie McDole, Yinan Wan, William C. Lemon, Dagmar Kainmueller, Philipp J. Keller, Stephan Preibisch, Jan Funke
Nature Biotechnology  ·  05 Sep 2022  ·  doi:10.1038/s41587-022-01427-7
Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning
Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning
Noah F. Greenwald, Geneva Miller, Erick Moen, Alex Kong, Adam Kagel, …, Sean C. Bendall, Leeat Keren, William Graf, Michael Angelo, David Van Valen
Nature Biotechnology  ·  10 Jan 2022  ·  doi:10.1038/s41587-021-01094-0
cell-lineage machine-learning
Mathematical and bioinformatic tools for cell tracking
Mathematical and bioinformatic tools for cell tracking
Peter Hirsch, Leo Epstein, Léo Guignard
Cell Movement in Health and Disease  ·  01 Jan 2022  ·  doi:10.1016/b978-0-323-90195-6.00013-9

2021

Automated Reconstruction of Whole-Embryo Cell Lineages by Learning from Sparse Annotations
Automated Reconstruction of Whole-Embryo Cell Lineages by Learning from Sparse Annotations
Caroline Malin-Mayor, Peter Hirsch, Leo Guignard, Katie McDole, Yinan Wan, William C. Lemon, Philipp J. Keller, Stephan Preibisch, Jan Funke
openRxiv  ·  29 Jul 2021  ·  doi:10.1101/2021.07.28.454016

2020

Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites
Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites
Jesse V. Veenvliet, Adriano Bolondi, Helene Kretzmer, Leah Haut, Manuela Scholze-Wittler, …, René Buschow, Lars Wittler, Bernd Timmermann, Alexander Meissner, Bernhard G. Herrmann
Science  ·  04 Dec 2020  ·  doi:10.1126/science.aba4937
gastruloids mouse
Contact area dependent cell communication and the morphological invariance of ascidian embryogenesis
Contact area–dependent cell communication and the morphological invariance of ascidian embryogenesis
Léo Guignard, Ulla-Maj Fiúza, Bruno Leggio, Julien Laussu, Emmanuel Faure, …, Kilian Biasuz, Lars Hufnagel, Grégoire Malandain, Christophe Godin, Patrick Lemaire
Science  ·  03 Jul 2020  ·  doi:10.1126/science.aar5663
ascidian morphogenesis cell-communication

2019

Evolution of embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians
Evolution of embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians
Alicia Madgwick, Marta Silvia Magri, Christelle Dantec, Damien Gailly, Ulla-Maj Fiuza, Léo Guignard, Sabrina Hettinger, Jose Luis Gomez-Skarmeta, Patrick Lemaire
Developmental Biology  ·  01 Apr 2019  ·  doi:10.1016/j.ydbio.2019.01.003
Quantitative analysis of animal morphogenesis : from high-throughput laser imaging to 4D virtual embryo in ascidians
Quantitative analysis of animal morphogenesis : from high-throughput laser imaging to 4D virtual embryo in ascidians
Montpellier University  ·  15 Jan 2019  ·  [no id info]

2018

In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level
In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level
Katie McDole, Léo Guignard, Fernando Amat, Andrew Berger, Grégoire Malandain, Loïc A. Royer, Srinivas C. Turaga, Kristin Branson, Philipp J. Keller
Cell  ·  04 Oct 2018  ·  doi:10.1016/j.cell.2018.09.031
mouse-embryo cell-tracking
Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.
Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.
Alicia Madgwick, Marta Silvia Magri, Christelle Dantec, Damien Gailly, Ulla-Maj Fiuza, Leo Guignard, Sabrina Hettinger, Jose Luis Gomez-Skarmeta, Patrick Lemaire
openRxiv  ·  19 Jul 2018  ·  doi:10.1101/371005
Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb
Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb
Carsten Wolff, Jean-Yves Tinevez, Tobias Pietzsch, Evangelia Stamataki, Benjamin Harich, …, Stephan Preibisch, Spencer Shorte, Philipp J Keller, Pavel Tomancak, Anastasios Pavlopoulos
eLife  ·  09 Apr 2018  ·  doi:10.7554/eLife.34410
cell-lineage arthropod
Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb
Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb
Carsten Wolff, Jean-Yves Tinevez, Tobias Pietzsch, Evangelia Stamataki, Benjamin Harich, …, Stephan Preibisch, Spencer Shorte, Philipp J Keller, Pavel Tomancak, Anastasios Pavlopoulos
eLife  ·  29 Mar 2018  ·  doi:10.7554/elife.34410

2017

Contact-dependent cell-cell communications drive morphological invariance during ascidian embryogenesis
Contact-dependent cell-cell communications drive morphological invariance during ascidian embryogenesis
Léo Guignard, Ulla-Maj Fiuza, Bruno Leggio, Emmanuel Faure, Julien Laussu, Lars Hufnagel, Grégoire Malandain, Christophe Godin, Patrick Lemaire
openRxiv  ·  24 Dec 2017  ·  doi:10.1101/238741

2015

Cell pairings for ascidian embryo registration
Cell pairings for ascidian embryo registration
Gael Michelin, Leo Guignard, Ulla-Maj Fiuza, Patrick Lemaire, Christophe Godine, Gregoire Malandain
2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)  ·  01 Apr 2015  ·  doi:10.1109/ISBI.2015.7163872
registration ascidian
Genome wide screen identifies a novel p97 CDC 48 dependent pathway regulating ER stress induced gene transcription
Genome‐wide screen identifies a novel p97/CDC‐48‐dependent pathway regulating ER‐stress‐induced gene transcription
Esther Marza, Saïd Taouji, Kim Barroso, Anne‐Aurélie Raymond, Léo Guignard, …, Martin E Fernandez‐Zapico, Jean Rosenbaum, Francesca Palladino, Denis Dupuy, Eric Chevet
The EMBO Reports  ·  06 Feb 2015  ·  doi:10.15252/embr.201439123
er-stress

2014

Spatio-temporal registration of embryo images
Spatio-temporal registration of embryo images
L. Guignard, C. Godin, U.-M. Fiuza, L. Hufnagel, P. Lemaire, G. Malandain
2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI)  ·  01 Apr 2014  ·  doi:10.1109/ISBI.2014.6867986
registration embryo
Embryo cell membranes reconstruction by tensor voting
Embryo cell membranes reconstruction by tensor voting
Gael Michelin, Leo Guignard, Ulla-Maj Fiuza, Gregoire Malandain
2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI)  ·  01 Apr 2014  ·  doi:10.1109/ISBI.2014.6868105
segmentation embryo

Quantitative analysis of animal morphogenesis : from high-throughput laser imaging to 4D virtual embryo in ascidians
Quantitative analysis of animal morphogenesis : from high-throughput laser imaging to 4D virtual embryo in ascidians
Léo Guignard
Agence Bibliographique de l'Enseignement Supérieur  ·  [no date info]  ·  doi:10.70675/c241b9a5z0a8az4591zbff9z7c3a20333422