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Corbacho, J.

Publications and source records attributed to Corbacho, J..

4 recordsLinked to original sources

Evolutionary landscapes of zygotic genome activation across animals

During early animal embryogenesis, gene expression control shifts from maternally deposited products to newly transcribed RNA through zygotic genome activation (ZGA). Although essential and universal, ZGA remains poorly understood outside a few model species. Here, we generated a transcriptomic atlas of early embryogenesis across 61 animal species from 13 phyla and used a unified computational framework to infer ZGA timing systematically. We find extensive variation in ZGA onset across animals, but show that the ratio between genome size and egg cytoplasmic volume, a proxy for the nuclear-to-cytoplasmic ratio, robustly predicts when genome activation begins. We also reveal that zygotic genes also differ from maternal transcripts in genomic architecture, function and evolutionary conservation, suggesting that ZGA follows a conserved molecular logic despite flexible transcriptomic outputs.

evolutionary biology↗

Single-cell multiomics identifies key nodes and cis-regulatory elements of the networks specifying the eye domains in zebrafish

Congenital eye malformations result from disruptions in the early developmental programs that specify and regionalize the eye primordium. Human genetics and developmental studies in animal models have identified critical regulatory nodes within the gene regulatory networks (GRNs) patterning the distinct eye domains. However, the fundamental cis-regulatory connectivity of these networks, and their dynamic behaviour, remains poorly understood. To address these gaps, we performed a comprehensive analysis of transcriptome dynamics and chromatin accessibility at single-cell resolution in the developing zebrafish forebrain. Our single-cell multiomic approach enabled us to characterize the regulatory landscape of the main eye derivatives: neural retina, optic stalk, pigmented epithelium and lens; alongside adjacent diencephalic and telencephalic regions. We identified and functionally validated tissue-specific cis-regulatory modules, and predicted highly connected nodes within each domain. Notably, we uncovered the role of foxp1b as a conserved central node within the neural retina network, highlighting the predictive power of our analysis in reconstructing the architecture of the GRNs that specify the vertebrate eye. TeaserIdentification of central nodes and cis-regulatory networks involved in eye patterning by single-cell multiomics in zebrafish.

developmental biology↗

HUMAN SPINAL CORD ORGANOIDS REVEAL CELL INTERCALATION AS A CONSERVED MECHANISM FOR SECONDARY NEURULATION

Human pluripotent stem cells (hPSCs) have enabled major advances in neural organoid research, yet reconstructing spinal cord development in vitro remains challenging, as it requires mimicking the early environment of body axis elongation. Here, by exposing hPSCs to defined extrinsic signals, we directed their self-organizing capacity to generate organoids that recapitulate the transcriptional profile, cellular composition, and tissue architecture of the early human posterior spinal cord. Furthermore, we refined our culture system to more closely model the in vivo morphogenetic events of secondary neurulation. Using this approach, we identified cell intercalation--regulated by Yes-associated protein (YAP) activity--as a key morphogenetic mechanism driving de novo lumen formation and resolution. These biomimetic models provide a powerful platform to investigate the molecular and mechanical processes underlying human spinal cord development and offer new opportunities to elucidate the origins of neural tube defects, among the most common congenital defects.

developmental biology↗

Trap-TRAP, a versatile tool for tissue-specific translatomics in zebrafish

Developmental and physiological processes depend on the transcriptional and translational activity of heterogeneous cell populations. A main challenge in gene expression studies is dealing with this intrinsic complexity while keeping sequencing efficiency. Translating ribosome affinity purification (TRAP) methods have allowed cell-specific recovery of polyribosome-associated RNAs by genetic tagging of ribosomes in selected cell populations. Here we combined the TRAP approach with adapted enhancer trap methods (trap-TRAP) to systematically generate zebrafish transgenic lines suitable for tissue-specific translatome interrogation. Through the random integration of the eGFP:rpl10a cassette, we have generated stable lines driving expression in a variety of tissues, including the retina, skeletal muscle, lateral line primordia, rhombomeres, or jaws. To increase the range of applications, a UAS:TRAP transgenic line compatible with available Gal4 lines was also generated and tested. The resulting collection of lines and applications constitutes a resource for the zebrafish community in developmental genetics, organ physiology and disease modelling.

developmental biology↗