| First Author | Chleilat E | Year | 2018 |
| Journal | Neuroscience | Volume | 381 |
| Pages | 124-137 | PubMed ID | 29689292 |
| Mgi Jnum | J:265050 | Mgi Id | MGI:6196841 |
| Doi | 10.1016/j.neuroscience.2018.04.019 | Citation | Chleilat E, et al. (2018) TGF-beta Signaling Regulates Development of Midbrain Dopaminergic and Hindbrain Serotonergic Neuron Subgroups. Neuroscience 381:124-137 |
| abstractText | Molecular 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-beta) during development of mDA and 5-HT subgroups. We have generated TbetaRII(flox/flox)::En1(cre/+) mice where type II TGF-beta receptor is conditionally deleted from engrailed 1-expressing cells and have investigated the hindbrain serotonergic system of these mice together with Tgf-beta2(-/-) mice. The results show a significant decrease in the number of 5-HT neurons in TGF-beta2-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-beta signaling from midbrain and rhombomere 1 leads to inactive TGF-beta 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-beta signaling during development of mDA and 5-HT subgroups, and suggest TGF-betas 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. |
