Multiple neural bHLHs ensure the precision of a neuronal specification event in Caenorhabditis elegans.
C. elegans
Neural bHLHs
Neuron
Robustness
Journal
Biology open
ISSN: 2046-6390
Titre abrégé: Biol Open
Pays: England
ID NLM: 101578018
Informations de publication
Date de publication:
15 12 2021
15 12 2021
Historique:
received:
03
08
2021
accepted:
22
11
2021
pubmed:
3
12
2021
medline:
5
4
2022
entrez:
2
12
2021
Statut:
ppublish
Résumé
Neural bHLH transcription factors play a key role in the early steps of neuronal specification in many animals. We have previously observed that the Achaete-Scute HLH-3, the Olig HLH-16 and their binding partner the E-protein HLH-2 activate the terminal differentiation program of a specific class of cholinergic neurons, AIY, in Caenorhabditis elegans. Here we identify a role for a fourth bHLH, the Neurogenin NGN-1, in this process, raising the question of why so many neural bHLHs are required for a single neuronal specification event. Using quantitative imaging we show that the combined action of different bHLHs is needed to activate the correct level of expression of the terminal selector transcription factors TTX-3 and CEH-10 that subsequently initiate and maintain the expression of a large battery of terminal differentiation genes. Surprisingly, the different bHLHs have an antagonistic effect on another target, the proapoptotic BH3-only factor EGL-1, normally not expressed in AIY and otherwise detrimental for its specification. We propose that the use of multiple neural bHLHs allows robust neuronal specification while, at the same time, preventing spurious activation of deleterious genes.
Identifiants
pubmed: 34854469
pii: 273578
doi: 10.1242/bio.058976
pmc: PMC8713986
pii:
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Caenorhabditis elegans Proteins
0
HLH-2 protein, C elegans
0
HLH-3 protein, C elegans
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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