• Enaam Chleilat, Lena Skatulla, Belal Rahhal, Manal T Hussein, Melanie Feuerstein, Kerstin Krieglstein, and Eleni Roussa.
• Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: enaam.chleilat@anat.uni-freiburg.de.
• Neuroscience. 2018 Jun 15; 381: 124-137.

AbstractMolecular and functional diversity within midbrain dopaminergic (mDA) and hindbrain serotonergic (5-HT) neurons has emerged as a relevant feature that could underlie selective vulnerability of neurons in clinical disorders. We have investigated the role of transforming growth factor beta (TGF-β) during development of mDA and 5-HT subgroups. We have generated TβRIIflox/flox::En1cre/+ mice where type II TGF-β receptor is conditionally deleted from engrailed 1-expressing cells and have investigated the hindbrain serotonergic system of these mice together with Tgf-β2-/- mice. The results show a significant decrease in the number of 5-HT neurons in TGF-β2-deficient mice at embryonic day (E) 12 and a selective significant decrease in the hindbrain paramedian raphe 5-HT neurons at E18, compared to wild type. Moreover, conditional deletion of TGF-β signaling from midbrain and rhombomere 1 leads to inactive TGF-β signaling in cre-expressing cells, impaired development of mouse mDA neuron subgroups and of dorsal raphe 5-HT neuron subgroups in a temporal manner. These results highlight a selective growth factor dependency of individual rostral hindbrain serotonergic subpopulations, emphasize the impact of TGF-β signaling during development of mDA and 5-HT subgroups, and suggest TGF-βs as potent candidates to establish diversity within the hindbrain serotonergic system. Thus, the data contribute to a better understanding of development and degeneration of mDA neurons and 5-HT-associated clinical disorders.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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