Ernest Arenas group

We study midbrain dopaminergic neuron development and stem cells and direct reprogramming for Parkinson’s disease (PD) cell replacement therapy and drug discovery.

Research areas

Midbrain dopaminergic neuron development

  • Characterizing the molecular cascades that regulate midbrain stem cell behavior as well as dopaminergic neurogenesis, differentiation and subtype specification.
  • The functions of Wnts, their receptors and their signaling pathways, with focus on new components of the Wnt/PCP signaling.
  • The function of nuclear receptors and their ligands in midbrain dopaminergic neuron development.
  • The identification of novel factors by single cell transcriptomic, proteomic and lipidomic approaches.
  • Control of midbrain dopaminergic neurogenesis by basic-helix-loop-helix transcription factors.

Stem cells and direct reprogramming for Parkinson’s disease (PD) cell replacement therapy and drug discovery

  • Improving protocols for the efficient differentiation of human stem cells (NES, ES, and iPS cells) into substantia nigra A9 dopaminergic neurons for cell replacement therapy and drug discovery.
  • Develop 2D and 3D in vitro models of midbrain tissue for PD drug discovery using human NES/ES/iPS cells with PD mutations and isogenic controls.
  • Examine the role of Wnt signaling in the pathogenesis of Parkinson’s disease.
  • Improve protocols for the direct in vitro reprogramming of somatic cells into substantia nigra A9 dopaminergic neurons.
  • Develop a novel cell replacement therapy for PD based on the direct in vivo reprogramming of striatal astrocytes in situ, into functional A9 dopaminergic neurons.


Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model.
Rivetti di Val Cervo P, Romanov RA, Spigolon G, Masini D, Martín-Montañez E, Toledo EM, et al
Nat. Biotechnol. 2017 05;35(5):444-452

Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells.
La Manno G, Gyllborg D, Codeluppi S, Nishimura K, Salto C, Zeisel A, et al
Cell 2016 Oct;167(2):566-580.e19

Supporting data and visualization

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease.
Villaescusa JC, Li B, Toledo EM, Rivetti di Val Cervo P, Yang S, Stott SR, et al
EMBO J. 2016 09;35(18):1963-78

Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.
Marques S, Zeisel A, Codeluppi S, van Bruggen D, Mendanha Falcão A, Xiao L, et al
Science 2016 Jun;352(6291):1326-1329

Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors.
Hedlund E, Belnoue L, Theofilopoulos S, Salto C, Bye C, Parish C, et al
Sci Rep 2016 06;6():26448

Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
Fukusumi Y, Meier F, Götz S, Matheus F, Irmler M, Beckervordersandforth R, et al
J. Neurosci. 2015 Sep;35(39):13385-401

Liver X receptors and cholesterol metabolism: role in ventral midbrain development and neurodegeneration.
Theofilopoulos S, Arenas E
F1000Prime Rep 2015 ;7():37

How to make a midbrain dopaminergic neuron.
Arenas E, Denham M, Villaescusa JC
Development 2015 Jun;142(11):1918-36

Cholestenoic acids regulate motor neuron survival via liver X receptors.
Theofilopoulos S, Griffiths WJ, Crick PJ, Yang S, Meljon A, Ogundare M, et al
J. Clin. Invest. 2014 Nov;124(11):4829-42

Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
Arenas E
J Mol Cell Biol 2014 Feb;6(1):42-53

Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons.
Yang S, Edman LC, Sánchez-Alcañiz JA, Fritz N, Bonilla S, Hecht J, et al
Development 2013 Nov;140(22):4554-64

Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
Andersson ER, Saltó C, Villaescusa JC, Cajanek L, Yang S, Bryjova L, et al
Proc. Natl. Acad. Sci. U.S.A. 2013 Feb;110(7):E602-10

Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis.
Theofilopoulos S, Wang Y, Kitambi SS, Sacchetti P, Sousa KM, Bodin K, et al
Nat. Chem. Biol. 2013 Feb;9(2):126-33

Complete list of publications at PubMed

Research group

Post-doctoral positions

Please, send your inquiries by e-mail to and include the following information:

  • CV with publications and research experience
  • A brief outline of research interests


Content reviewer:
Sara Lidman