ArticleBiology open2016
Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function.
Article in Biology open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.Stem cells translational medicine · 2023Article
- Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons.International journal of molecular sciences · 2022Review
- Article
- Acquisition of the Midbrain Dopaminergic Neuronal Identity.International journal of molecular sciences · 2020Review
- Review
- EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.Frontiers in molecular neuroscience · 2019Article
- Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research.Current opinion in neurobiology · 2018Review
- Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool.PloS one · 2017Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The isthmic organizer (IsO) is a signaling center that specifies the correct and distinct embryonic development of the dopaminergic midbrain and serotonergic hindbrain. The IsO is a linear boundary between the two brain regions, emerging at around embryonic day 7-8 of murine embryonic development, that shapes its surroundings through the expression of instructive signals such as Wnt and growth factors. Homeobox transcription factor engrailed 1 (En1) is present in midbrain and rostral hindbrain (i.e. rhombomere 1, R1). Its expression spans the IsO, and it is known to be an important survival factor for both dopaminergic and serotonergic neurons. Erroneous composition of dopaminergic neurons in the midbrain or serotonergic neurons in the hindbrain is associated with severe pathologies such as Parkinson's disease, depression or autism. Here we investigated the role of En1 in early mid-hindbrain development, using multiple En1-ablated mouse models as well as lineage-tracing techniques, and observed the appearance of ectopic dopaminergic neurons, indistinguishable from midbrain dopaminergic neurons based on molecular profile and intrinsic electrophysiological properties. We propose that this change is the direct result of a caudal relocation of the IsO as represented by ectopic presence of Fgf8, Otx2, Wnt1 and canonical Wnt-signalling. Our work suggests a newly-discovered role for En1: the repression of Otx2, Wnt1 and canonical Wnt-signaling in R1. Overall, our results suggest that En1 is essential for proper IsO maintenance and function.
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