Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function.

Yinan Li,Paschalis Kratsios,Munachiso A Okebalama,André Ex Brown,Olivia Gaylord,Anthony Osuma,Jihad Aburas,Edgar Correa,Pauline Dao,Priota Islam

doi:10.7554/elife.59464

Abstract

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.

Highlights

Nervous system development is a multi-step process that culminates in the generation of distinct neuron types necessary for animal behavior
Is temporal modularity observed in the function of other terminal selectors? To address this, we focused on UNC-30/PITX, the terminal selector of GABAergic motor neurons (MNs) (DD, VD) identity in the C. elegans nerve cord (Figure 7A; Jin et al, 1994)
Using reporter strains and methodologies similar to those used for UNC-3, we found that terminal identity gene expression is affected in GABAergic MNs of unc-30 mutants at all stages examined (3-fold embryo, larval stage 2 (L2), larval stage 4 (L4), adult [day 1]) (Figure 7B,D), suggesting a requirement for initiation and maintenance

Summary

Introduction

Nervous system development is a multi-step process that culminates in the generation of distinct neuron types necessary for animal behavior. Seminal studies in many model systems have begun to elucidate the molecular mechanisms that control the early steps of neuronal development, such as specification of neural progenitors and generation of post-mitotic neurons (Catela and Kratsios, 2019; Doe, 2017; Greig et al, 2013; Jessell, 2000; Lodato and Arlotta, 2015; Perry et al, 2017). Once neurons become post-mitotic, how do they acquire their unique functional features, such as neurotransmitter synthesis, electrical activity and signaling properties? Terminal selectors represent one class of transcription factors (TFs) with continuous expression – from development through adulthood – in specific neuron types (Hobert, 2008; Hobert, 2011; Hobert, 2016b; Garcıa-Bellido, 1975).

Methods

Results

Conclusion