Department of Neurobiology; Alkema Lab
During development, signal-regulated transcription factors (TFs) act as basal repressors and upon signalling through morphogens or cell-to-cell signalling shift to activators, mediating precise and transient responses. Conversely, at the final steps of neuron specification, terminal selector TFs directly initiate and maintain neuron-type specific gene expression through enduring functions as activators. C. elegans contains 3 types of serotonin synthesising neurons that share the expression of the serotonin biosynthesis pathway genes but not of other effector genes. Here, we find an unconventional role for LAG-1, the signal-regulated TF mediator of the Notch pathway, as terminal selector for the ADF serotonergic chemosensory neuron, but not for other serotonergic neuron types. Regulatory regions of ADF effector genes contain functional LAG-1 binding sites that mediate activation but not basal repression. lag-1 mutants show broad defects in ADF effector genes activation, and LAG-1 is required to maintain ADF cell fate and functions throughout life. Unexpectedly, contrary to reported basal repression state for LAG-1 prior to Notch receptor activation, gene expression activation in the ADF neuron by LAG-1 does not require Notch signalling, demonstrating a default activator state for LAG-1 independent of Notch. We hypothesise that the enduring activity of terminal selectors on target genes required uncoupling LAG-1 activating role from receiving the transient Notch signalling.
Neurons, RNA interference, Gene expression, Neuronal differentiation, Young adults, Notch signaling, Serotonin, Neuronal plasticity
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Copyright © 2021 Maicas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Maicas M, Jimeno-Martín Á, Millán-Trejo A, Alkema MJ, Flames N. The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate maintenance, and plasticity of serotonergic chemosensory neurons. PLoS Biol. 2021 Jul 7;19(7):e3001334. doi: 10.1371/journal.pbio.3001334. PMID: 34232959; PMCID: PMC8289040. Link to article on publisher's site
Maicas M, Jimeno-Martin A, Millan-Trejo A, Alkema MJ, Flames N. (2021). The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate maintenance, and plasticity of serotonergic chemosensory neurons. UMass Chan Medical School Faculty Publications. https://doi.org/10.1371/journal.pbio.3001334. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2174
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