A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life
Weidong Feng,
Yinan Li,
Pauline Dao,
Jihad Aburas,
Priota Islam,
Benayahu Elbaz,
Anna Kolarzyk,
André EX Brown,
Paschalis Kratsios
Affiliations
Weidong Feng
Department of Neurobiology, University of Chicago, Chicago, United States; Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, United States
Yinan Li
Department of Neurobiology, University of Chicago, Chicago, United States; Committee on Neurobiology, University of Chicago, Chicago, United States
Pauline Dao
Department of Neurobiology, 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
Benayahu Elbaz
Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, United States
Anna Kolarzyk
Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, United States
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 Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, United States; Committee on Neurobiology, University of Chicago, Chicago, United States; The Grossman Institute for Neuroscience, Quantitative Biology, and Human Behavior, University of Chicago, Chicago, United States
To become and remain functional, individual neuron types must select during development and maintain throughout life their distinct terminal identity features, such as expression of specific neurotransmitter receptors, ion channels and neuropeptides. Here, we report a molecular mechanism that enables cholinergic motor neurons (MNs) in the C. elegans ventral nerve cord to select and maintain their unique terminal identity. This mechanism relies on the dual function of the conserved terminal selector UNC-3 (Collier/Ebf). UNC-3 synergizes with LIN-39 (Scr/Dfd/Hox4-5) to directly co-activate multiple terminal identity traits specific to cholinergic MNs, but also antagonizes LIN-39’s ability to activate terminal features of alternative neuronal identities. Loss of unc-3 causes a switch in the transcriptional targets of LIN-39, thereby alternative, not cholinergic MN-specific, terminal features become activated and locomotion defects occur. The strategy of a terminal selector preventing a transcriptional switch may constitute a general principle for safeguarding neuronal identity throughout life.
