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  Serotonin Receptor 2A Activation Promotes Evolutionarily Relevant Basal Progenitor Proliferation in the Developing Neocortex.

Xing, L., Kalebic, N., Namba, T., Vaid, S., Wimberger, P., & Huttner, W. (2020). Serotonin Receptor 2A Activation Promotes Evolutionarily Relevant Basal Progenitor Proliferation in the Developing Neocortex. Neuron, 108(6), 1113-1129. doi:10.1016/j.neuron.2020.09.034.

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 Creators:
Xing, Lei1, Author           
Kalebic, Nereo1, Author           
Namba, Takashi1, Author           
Vaid, Samir1, Author           
Wimberger, Pauline, Author
Huttner, Wieland1, Author           
Affiliations:
1Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: Evolutionary expansion of the mammalian neocortex (Ncx) has been linked to increased abundance and proliferative capacity of basal progenitors (BPs) in the subventricular zone during development. BP proliferation is governed by both intrinsic and extrinsic signals, several of which have been identified. However, a role of neurotransmitters, a canonical class of extrinsic signaling molecules, in BP proliferation remains to be established. Here, we show that serotonin (5-HT), via its receptor HTR2A, promotes BP proliferation in an evolutionarily relevant manner. HTR2A is not expressed in embryonic mouse Ncx; accordingly, 5-HT does not increase mouse BP proliferation. However, ectopic HTR2A expression can increase mouse BP proliferation. Conversely, CRISPR/Cas9-mediated knockout of endogenous HTR2A in embryonic ferret Ncx reduces BP proliferation. Pharmacological activation of endogenous HTR2A in fetal human Ncx ex vivo increases BP proliferation via HER2/ERK signaling. Hence, 5-HT emerges as an important extrinsic pro-proliferative signal for BPs, which may have contributed to evolutionary Ncx expansion.

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 Dates: 2020-10-09
 Publication Status: Issued
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 Identifiers: DOI: 10.1016/j.neuron.2020.09.034
Other: cbg-7837
PMID: 33080227
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Title: Neuron
  Other : Neuron
Source Genre: Journal
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Pages: - Volume / Issue: 108 (6) Sequence Number: - Start / End Page: 1113 - 1129 Identifier: -