Dario Acampora

Dario Acampora

Research Director

  +39 081 6132 443/441   dario.acampora@igb.cnr.it

Embryonic Development and Biology of Stem Cells – Neurobiology and Brain Functioning

Keywords: Parkinson’s disease, mouse modeling, Embryonic stem cells

Focus. The research focus in our lab is on the genetic modeling of Parkinson’s disease in the mouse.

Research. Over the past, our laboratory has contributed to the understanding of molecular mechanisms that underlie normal and pathological brain development by employing the Otx genes and transgenic mice as genetic model systems. These genes embryonically govern proper specification and patterning of the brain areas, and their altered expression in adulthood can cause neurological and sense organ diseases. Importantly, we discovered that Otx2 is a crucial genetic determinant of a subset of dopaminergic neurons of the ventral tegmental area (VTA), which are also characterised by resistance to spontaneous and induced neurodegeneration. Intriguingly, Otx2 is sufficient to antogonise molecular and functional features of other dopaminergic neuron subtypes, including those of the substantia nigra pars compacta (SNpc), for which its forced expression can provide protection from induced neurodegeneration.

More recently, through mutant models, both in vivo and in vitro, we unveiled new Otx2 functions,  within the gene network controlling different states of cellular pluripotency and exit from it.  Among the most striking ones is the Otx2 dependent cell fate choice leading to the segregation of germ line from soma.

Research project. Over the last couple of years our research has moved back to neuroscience and Parkinson’s disease (PD) in particular. PD is characterized by the loss of dopaminergic neurons of the SNpc associated with high genetic and phenotypic heterogeneity. Thanks to a collaboration with an IGB geneticist (Dr. T. Esposito), a large number of disrupting variants in 26 candidate genes associated with late onset PD (LOPD) has recently been identified. Of note, the co-inheritance of multiple rare variants (≥ 2) in these 26 genes could predict PD occurrence in about 20% of patients, with high specificity. In order to validate a causal relationship between mutation(s) and disease and with the intent to model PD complexity, we have generated a series of humanized transgenic mouse lines replicating some of the genetic mutations found in patients, also in combination. These lines will undergo molecular, cellular and behavioural investigation for both spontaneous (with aging) and induced neurodegeneration and may represent prospective tools of preclinical relevance.

– Gialluisi, A., Reccia, M. G., Modugno, N., Nutile, T., Lombardi, A., Di Giovannantonio, L. G., Pietracupa, S., Ruggiero, D., Scala, S., Gambardella, S., International Parkinson’s Disease Genomics Consortium (IPDGC), Iacoviello, L., Gianfrancesco, F., Acampora, D., D’Esposito, M., Simeone, A., Ciullo, M., & Esposito, T.

Identification of sixteen novel candidate genes for late onset Parkinson’s disease. Molecular neurodegeneration, 16(1), 35. https://doi.org/10.1186/s13024-021-00455-2, (2021).

– Di Giovannantonio, LG.*, Acampora, D.*, Omodei, D., Nigro, V., Barba, P., Barbieri, E., Chambers, I. and Simeone, A.

Direct repression of Nanog and Oct4 by OTX2 modulates contribution of epiblast-derived cells to germline and somatic lineage. Development, 148(10), https://doi.org/10.1242/dev.199166 (2021).

– Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., Chambers, I.

OTX2 restricts entry to the mouse germline. Nature. 562, 595-599 (2018).

– Acampora, D., Omodei, D., Petrosino, G., Garofalo, A., Savarese, M., Nigro, V., Di Giovannantonio, L.G., Mercadante, V., Simeone, A.

Loss of the Otx2 binding site in the Nanog promoter affects the integrity of embryonic stem cell subtypes and specification of inner cell mass-derived epiblast. Cell Rep. 15, 2651-2664 (2016).

– Buecker, C., Srinivasan, R., Wu, Z., Calo, E., Acampora, D., Faial, T., Simeone, A., Tan, M., Swigut, T., Wysocka,J.

Enhancer reorganization in transition from naïve to primed pluripotency. Cell Stem Cell 14, 838-853 (2014).

– Acampora, D., Di Giovannantonio L.G., Simeone, A.

Otx2 is an intrinsic determinant of the Embryonic Stem Cell state and is required for transition to a stable Epiblast Stem Cell condition. Development, 140, 43-55 (2013).

– Di Salvio, M., Di Giovannantonio, LG., Acampora, D., Prosperi, R., Omodei, D., Prakash, N., Wurst, W., Simeone, A.

Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP.

Nature Neuroscience. 13, 1481-1488 (2010).

–  Puelles, E.*, Acampora, D. *, Lacroix, E.*, Signore, M., Annino, A., Tuorto, F., Filosa, S., Corte, G., Wurst, W., Ang, S.L.  & Simeone, A.

Otx dose-dependent integrated control of antero-posterior and dorso-ventral patterning of midbrain. Nature Neuroscience 6, 453-460 (2003).

– Acampora, D., Pilo Boyl, P., Signore, M., Martinez-Barbera, J.P., Ilengo, C., Puelles, E., Annino, A., Reichert, H., Corte, G. & Simeone, A.

OTD/OTX2 functional equivalence depends on 5’ and 3’ UTR-mediated control of Otx2 mRNA for nucleo-cytoplasmic export and epiblast-restricted translation. Development 128, 4801-4813 (2001).

– Acampora, D., Postiglione, M.P., Avantaggiato, V., Di Bonito, M., Vaccarino, F., Michaud, J. & Simeone, A.

Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Genes & Development 13, 2787-800 (1999).

– Acampora, D., Mazan, S., Avantaggiato, V., Barone, P., Tuorto, F., Lallemand, Y., Brûlet, P. & Simeone, A.

Epilepsy and brain abnormalities in mice lacking the Otx1 gene. Nature Genetics 14, 218-222 (1996).

– Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury, M., Simeone, A. & Brûlet, P.

Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121, 3279-3290 (1995).

– Acampora. D., D’Esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F., Stornaiuolo, E., Nigro, V., Simeone, A. & Boncinelli, E.

The human HOX gene family. Nucl. Acids. Res. 17, 10385-10402 (1989).

– Mavilio, F., Simeone, A., Giampaolo, A., Faiella, A., Zappavigna, V., Acampora, D., Poiano, G., Russo, G., Peschle, C. & Boncinelli, E.

Differential and stage-related expression in embryonic tissue of a new human homeo-box gene.  Nature 324, 664-668 (1986).

Appointments and scientific career

  • 2010 to present: IGB-CNR, Research Director (Dirigente di Ricerca)
  • 2006:   IGB-CNR, Senior Research Scientist (Primo Ricercatore)
  • 2001: IGB-CNR, Research Scientist (Ricercatore)
  • 2000-05: MRC Senior Non-Clinical Fellow at the MRC Centre for Developmental Neurobiology. King’s College London, London (UK).
  • 2000: Senior Lecturer, Developmental Neurobiology. King’s College London (UK).
  • 1999- 2004: C.N.R. staff scientist, five-year contract at the I.I.G.B.-Naples.
  • 1994- 99: C.N.R. staff scientist, five-year contract at the I.I.G.B.-Naples.
  • 1993- 94: EMBO long-term fellow. Institut Pasteur, Paris (FR).
  • 1991- 93: CNR (MISM) research fellow. Project entitled: “Biotechnologies and Molecular Biology Project”.
  • 1989- 90: CNR research fellow. Project entitled: “Mapping and Sequencing of Human Genome Project”.
  • 1988- 89: “Fondazione Anna Villa Rusconi” research fellow.
  • 1987:   Graduated in Biology with honours at the University of Naples. Tesis entitled: ”Genomic structure and embryonic expression of two human homeotic genes”.


Professional activities

  • 2020 to present: Modeling Parkinson’s disease through “humanized” mouse mutants.
  • 2013 to present: Scientific manager of the “Embryonic Stem Cells and Mouse Modeling (SCMM) facility” at IGB-ABT (http://mousemodeling.igb.cnr.it/)
  • 2018-20: Role of Otx2 in Primordial Germ Cells, both in vitro and in vivo.
  • 2013-17: Roles of Otx2 in the pluripotency regulatory network: identification of target genes through combined analysis of RNA/ChIP-seq, ChIP and Otx2 binding site mutagenesis both in vitro and in vivo. Generation and analysis of mutant ESC lines        addressing the Otx2/Nanog genetic interaction.
  • 2009-12: CEINGE Biotecnologie Avanzate, Naples (in partnership with IGB)

Role of Otx2 gene in mouse Embryonic Stem Cells and their differentiation towards different cell-types. Role of Otx2 gene in epiblast explants and Embryonic Stem Cell-Derived Epiblast Stem Cells (ESD-EpiSC).

  • 2005-09: CEINGE Biotecnologie Avanzate, Naples (in partnership with IGB)

Conditional knock-down and up-regulation of Otx genes expression in mouse models using an inducible system. Focus on dopaminergic progenitors and post-mitotic neurons.

  • 2000-05: KCL, UK. Functional studies on the role of the Otx genes in midbrain patterning. Functional “evo/devo” studies on Otx genes through the generation of transgenic mouse models addressing cross-phylum functional equivalence.
  • 1995- 99: Orthopedia (Otp) gene null mice and analysis of Otp function in the neuroendocrine axis. Assessment of Otx1/Otx2 gene dosage requirement and functional equivalence.
  • 1993- 94: Homologous recombination in ES cells and generation of Otx1 and Otx2 null mice (Institut Pasteur. Paris, FR).
  • 1991- 93: Molecular characterization and expression of a new family of brain-specific homeobox containing genes (Otx and Emx).
  • 1985- 90: Isolation and molecular characterization of homeobox containing genes clustered in the HOX1, HOX2, HOX3 and HOX4 loci (genomic collinearity). Human HOX genes in the retinoic acid inducible EC cells system (temporal collinearity).