- Self-sabotage in the early mammalian embryo: investigating the interplay between DNA damage responses, splicing failure and zygotic reprogramming. 01/06/2025 to 30/05/2030. ERC Consolidator Grant 2024. (101171650-EARLYFATE) – 1.993.143,00 EUR. PI: Dr. Bárbara Pernaute.
- DNA damage responses during zygotic genome activation and reprogramming to totipotency. 09/2023 to 08/2027. PID2022-137086NB-I00 – 192.500,00 EUR. PI: Dr. Bárbara Pernaute
- Regulation of death and differentiation in the early mammalian embryo. 01/2023 to 12/2027. RYC2021-031897-I. 236.350,00EUR (includes salary). PI: Dr. Bárbara Pernaute
GROUP DESCRIPTION
In mammals, fertilization involves the fusion of two fully differentiated cells, the gametes, whose genomes undergo a profound epigenetic reprogramming to become a totipotent embryo with the capacity to form all lineages, both embryonic and extraembryonic. This epigenetic reprogramming is closely associated with the transition from maternal to zygotic control of gene expression during Zygotic Genome Activation. Cell potency then gets gradually restricted, first with the specification of the extraembryonic lineages and later through the formation of the germline and three germ layers which will give rise to the foetus itself.
Our group is interested in studying the gene regulatory networks underlying these early stages of mammalian development, with a focus on transcriptional and post-transcriptional regulation of gene expression, cell fate decisions and genome integrity control, which is particularly critical at a point when any cell has the capacity to contribute to the embryo and the germ line.
We also have a keen interest in understanding early developmental processes in the context of mammalian evolution, as many of the events that take place at these early stages are conditioned by the mammal-specific need to form extraembryonic structures to support in utero embryo growth
GROUP OBJECTIVES
The main research interest of the lab is understanding the molecular mechanisms governing the cellular reprogramming that occurs after fertilisation and that converts the transcriptionally inactive zygote into a transcriptionally active totipotent embryo capable of forming all cell lineages. For this we focus not only on the study of processes historically associated with developmental biology like transcriptional regulation, but also on the role played by the mechanisms that regulate homeostasis maintenance, such as genome integrity control and RNA splicing regulation.
RESEARCH GROUP MEMBERS







RESEARCH LINES
- Crosstalk between DNA damage response pathways and early development processes such as zygotic genome activation and totipotency acquisition and loss.
- Impact of nuclear organization on genome regulation during early mammalian development.
- Regulation of cell fate transitions in the early embryo in the context of mammalian evolution.
PROJECTS
PUBLICATIONS
- Wei X*, Salvador-Martinez I*, Meglicki M*, Plana-Carmona M*, Klonizakis A*, Pernaute B, Irimia M, Stik G, Popovic M, Torcal Garcia G, Heyn H, Zernicka-Goetz M†, Graf T† (2025). Role of CEBPa in trophectoderm competence installment. Sci Adv. Nov 28;11(48):eady1693. doi: 10.1126/sciadv.ady1693
- Zaffagnini G, Cheng S, Salzer MC, Pernaute B, Duran JM, Irimia M, Schuh M, Böke E† (2024). Mouse oocytes sequester aggregated proteins in degradative super-organelles. Cell. Feb 9:S0092-8674(24)00068-0. DOI: 10.1016/j.cell.2024.01.031
- Pernaute B*, Pérez-Montero S*, Sanchez-Nieto JM*, di Gregorio A, Lima A,…, Rodríguez TA† (2022). DRP1 levels determine the apoptotic threshold during embryonic differentiation through a mitophagy-dependent mechanism. Dev Cell. June 6;57(11):1316-1330.e7. DOI: 10.1016/j.devcel.2022.04.020
- Wyatt CDR*, Pernaute B*†, Gohr A,…, Irimia M† (2022). A developmentally programmed splicing failure contributes to DNA damage response attenuation during mammalian zygotic genome activation. Sci Adv Apr 15;8(15):eabn4935. DOI: 10.1126/sciadv.abn4935
- Spruce T, Plass M, Gohr A,…, Pernaute B† and Irimia M† (2022). The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians. Plos Biol Apr27;20(4):e3001615. doi.org/10.1371/journal.pbio.3001615
- Pernaute B, Spruce T, Smith KM, Sanchez-Nieto JM, Manzanares M, Cobb B and Rodriguez TA† (2014). MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM. Genes & Dev. Sep 1;28(17):1873-8. DOI: 10.1101/gad.245621.114
- Sancho M*, Di-Gregorio A*, George N*, Pozzi S, Sanchez JM, Pernaute B, Rodriguez TA† (2013). Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev Cell. 26(1):19-30 DOI: 10.1016/j.devcel.2013.06.012
- Clements M, Pernaute B, Vella F, Rodriguez TA† (2011). Crosstalk between Nodal/activin and MAPK p38 signaling is essential for anterior-posterior axis specification. Curr Biol. 21(15):1289-95. DOI: 10.1016/j.cub.2011.06.048
- Spruce T*, Pernaute B*, Di-Gregorio A, Cobb B, Merkenschlager M, Manzanares M†, Rodríguez TA† (2010). An early developmental role for miRNAs in the maintenance of extra-embryonic stem cells in the mouse embryo. Dev Cell. 19(2):207-19 DOI: 10.1016/j.devcel.2010.07.014
- Pernaute B, Cañon S, Crespo M, Fernandez-Tresguerres B, Rayon T, Manzanares M† (2010). Comparison of extraembryonic expression of Eomes and Cdx2 in pregastrulation chick and mouse embryo unveil regulatory changes along evolution. Dev Dyn. 239(2):620-9. DOI: 10.1002/dvdy.22176