Gene regulation and morphogenesis
Cell heterogeneity and tissue patterning
DRA Christina Paliou
ResearcherSummary
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).
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).
