Abstract
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-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 significant decrease in the number
of 5-HT neurons in TGF-2 deficient mice at embryonic day (E) 12 and a selective significant
decrease of the hindbrain paramedian raphe 5-HT neurons at E18, compared to wild type.
Moreover, conditional deletion of TGF-β signalling from midbrain and rhombomere 1 leads
to inactive TGF- 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 signalling during development
of mDA and 5-HT subgroups, and suggest TGF-s 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.

Title

Neuroscience

Publisher

Elsevier Ltd

Publisher Country

Netherlands

Indexing

Thomson Reuters

Impact Factor

0.552

Publication Type

Prtinted only

Volume

381

Year

2018

Pages

124-137