ArticlePloS one2017
Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- The Role of Purine Metabolism and Uric Acid in Postnatal Neurologic Development.Molecules (Basel, Switzerland) · 2025Review
- Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons.Neural regeneration research · 2024Article
- The Crucial Roles of Pitx3 in Midbrain Dopaminergic Neuron Development and Parkinson's Disease-Associated Neurodegeneration.International journal of molecular sciences · 2023Review
- From 2D to 3D: Development of Monolayer Dopaminergic Neuronal and Midbrain Organoid Cultures for Parkinson's Disease Modeling and Regenerative Therapy.International journal of molecular sciences · 2023Review
- Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons.International journal of molecular sciences · 2022Review
- HOX cluster and their cofactors showed an altered expression pattern in eutopic and ectopic endometriosis tissues.Reproductive biology and endocrinology : RB&E · 2021Article
- Neural tube patterning: from a minimal model for rostrocaudal patterning toward an integrated 3D model.iScience · 2021Article
- Acquisition of the Midbrain Dopaminergic Neuronal Identity.International journal of molecular sciences · 2020Review
- Review
- Article
- BMP/SMAD Pathway and the Development of Dopamine Substantia Nigra Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population.
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