Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function
Yinan Li,
Anthony Osuma,
Edgar Correa,
Munachiso A Okebalama,
Pauline Dao,
Olivia Gaylord,
Jihad Aburas,
Priota Islam,
André EX Brown,
Paschalis Kratsios
Affiliations
Yinan Li
Department of Neurobiology, University of Chicago, Chicago, United States; Committee on Neurobiology, University of Chicago, Chicago, United States
Anthony Osuma
Department of Neurobiology, University of Chicago, Chicago, United States; Committee on Neurobiology, University of Chicago, Chicago, United States
Edgar Correa
Department of Neurobiology, University of Chicago, Chicago, United States; Cell and Molecular Biology Program, University of Chicago, Chicago, United States
Munachiso A Okebalama
Department of Neurobiology, University of Chicago, Chicago, United States
Pauline Dao
Department of Neurobiology, University of Chicago, Chicago, United States
Olivia Gaylord
Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, United States
Jihad Aburas
Department of Neurobiology, University of Chicago, Chicago, United States
Priota Islam
MRC London Institute of Medical Sciences, London, United Kingdom; Institute of Clinical Sciences, Imperial College London, London, United Kingdom
André EX Brown
MRC London Institute of Medical Sciences, London, United Kingdom; Institute of Clinical Sciences, Imperial College London, London, United Kingdom
Department of Neurobiology, University of Chicago, Chicago, United States; Committee on Neurobiology, University of Chicago, Chicago, United States; Cell and Molecular Biology Program, University of Chicago, Chicago, United States; Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, United States; The Grossman Institute for Neuroscience, Quantitative Biology, and Human Behavior, University of Chicago, Chicago, United States
Terminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of C. elegans cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing ‘temporal modularity’ in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g. receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3’s temporal modularity via genome engineering affects locomotion. Another C. elegans terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.
