Genome Dynamics

Cell heterogeneity and tissue patterning

Dra Christina Paliou

 Researcher

Summary

Our lab investigates the gene regulatory dynamics that drive cellular heterogeneity and tissue patterning during vertebrate development. Gene regulation orchestrates the precise spatiotemporal expression of genes, acting through a multilayered system involving transcription factors, cis-regulatory elements, chromatin state, and post-transcriptional mechanisms. These components form gene regulatory networks (GRNs) that integrate both intrinsic programs and extrinsic signals to specify cell identity, guide differentiation, and coordinate morphogenesis.
We focus on dissecting the GRNs that shape cellular and spatial diversity in the developing fins of the small-spotted catshark (Scyliorhinus canicula), a representative of a basal vertebrate lineage. By comparing these ancestral appendages to tetrapod limbs, we aim to uncover the genomic and regulatory innovations that underlie the emergence of new morphological traits.
To address these questions, we employ a multi-modal approach that integrates single-cell omics, spatial transcriptomics, functional genomics, chromatin conformation capture techniques, zebrafish transgenic assays alongside classic molecular tools.
Our goals are to:
-Determine how similar GRNs can generate different tissue patterns, and whether cellular heterogeneity drives this divergence
-Explore how cell state variability and regulatory plasticity are modulated across evolutionary contexts
-Identify shifts in gene regulatory logic or cell identity landscapes that may have contributed to the fin-to-limb transition in vertebrates
In a broader context, our research seeks to reveal how gene regulation governs developmental complexity, with implications for understanding the origins of congenital disorders and the evolution of vertebrate body plans.

Figure 1.
A. The small-spotted catshark as a model to study the cellular and spatial diversity in developing fins.
B. Single-cell atlas of the developing fins of the catshark presenting the principal cluster groups; mesenchyme, muscle, and skin (left panel). Visualization of a muscle progenitor marker (ScPax3), a proximal mesenchyme marker (ScMeis2) and a posterior mesenchyme marker (ScHand2) expression in st.31 catshark pectoral fin by HCR (right panel).
C. Single-cell ATAC-seq pinpoints differentially accessible regions (DARs, white boxes) potentially controlling gene X expression between muscle and mesenchymal (Mesen) cell populations of pectoral (Pec) and pelvic (Pel) fins (left panel). Selected DARs tested with enhancer reporter assays in vivo in zebrafish (right panel).

Relevant literature

  • Ferdinand Marlétaz*, Elisa de la Calle-Mustienes*, Rafael D Acemel*, Christina Paliou*, Silvia Naranjo, Pedro Manuel Martínez-García, Ildefonso Cases, Victoria A Sleight, Christine Hirschberger, Marina Marcet-Houben, Dina Navon, Ali Andrescavage, Ksenia Skvortsova, Paul Edward Duckett, Álvaro González-Rajal, Ozren Bogdanovic, Johan H Gibcus, Liyan Yang, Lourdes Gallardo-Fuentes, Ismael Sospedra, Javier Lopez-Rios, Fabrice Darbellay, Axel Visel, Job Dekker, Neil Shubin, Toni Gabaldón, Tetsuya Nakamura, Juan J Tena, Darío G Lupiáñez, Daniel S Rokhsar, José Luis Gómez-Skarmeta (2023). The little skate genome and the evolutionary emergence of wing-like fins. Nature 616, 495–503.

  • Christina Paliou, Philine Guckelberger, Robert Schöpflin, Verena Heinrich, Andrea Esposito, Andrea M Chiariello, Simona Bianco, Carlo Annunziatella, Johannes Helmuth, Stefan Haas, Ivana Jerković, Norbert Brieske, Lars Wittler, Bernd Timmermann, Mario Nicodemi, Martin Vingron, Stefan Mundlos, Guillaume Andrey (2019). Preformed chromatin topology assists transcriptional robustness of Shh during limb development. Proc. Natl. Acad. Sci. U. S. A. 116, 12390–12399.

  • Bjørt K Kragesteen*, Malte Spielmann*, Christina Paliou, Verena Heinrich, Robert Schöpflin, Andrea Esposito, Carlo Annunziatella, Simona Bianco, Andrea M Chiariello, Ivana Jerković, Izabela Harabula, Philine Guckelberger, Michael Pechstein, Lars Wittler, Wing-Lee Chan, Martin Franke, Darío G Lupiáñez, Katerina Kraft, Bernd Timmermann, Martin Vingron, Axel Visel, Mario Nicodemi, Stefan Mundlos, Guillaume Andrey. Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis. Nature Genetics. 50, 1463–1473.

    Full list of articles here. 

Lab members & collaborators

 

Associated Investigator

Dr. Christina Paliou

 

Technician/Lab manager

Dr. Sara María Ortega Campos (shared position with Dr. Martin Franke)

 

Collaborators

Dr. Sylvie Mazan (Observatoire Oceanologique-CNRS, Banyuls-sur-Mer, France)
Dr. Dario Lupiañez (CABD, Seville, Spain)
Dr. Christian Feregrino (MPIMG, Berlin, Germany)
Dr. Francisca Martinez Real (CABD, Seville, Spain)

Alumni

Dr. Elisa Suarez Martinez, Research Assistant