Piecemeal regulation of convergent neuronal lineages by bHLH transcription factors inCaenorhabditis elegans

Abstract

Cells of the same type can be generated by distinct cellular lineages that originate in different parts of the developing embryo (‘lineage convergence’). Several Caenorhabditis elegans neuron classes composed of left/right or radially symmetric class members display such lineage convergence. We show here that the C. elegans Atonal homolog lin-32 is differentially expressed in neuronal lineages that give rise to left/right or radially symmetric class members. Loss of lin-32 results in the selective loss of the expression of pan-neuronal markers and terminal selector-type transcription factors that confer neuron class-specific features. Another basic helix-loop-helix (bHLH) gene, the Achaete-Scute homolog hlh-14, is expressed in a mirror image pattern relative to lin-32 and is required to induce neuronal identity and terminal selector expression on the contralateral side of the animal. These findings demonstrate that distinct lineage histories converge via different bHLH factors at the level of induction of terminal selector identity determinants, which thus serve as integrators of distinct lineage histories. We also describe neuron-to-neuron identity transformations in lin-32 mutants, which we propose to also be the result of misregulation of terminal selector gene expression.

Transcriptional regulation of neuronal identity

“…In the progenitor, spatial/lineage TFs work together with proneural TFs, a specific set of bHLH TFs with conserved functions in mouse, Drosophila and C. elegans. Proneural TFs are necessary, and in some contexts sufficient, to induce neuronal fates (Figure 2) (Baker & Brown, 2018;Dennis et al, 2019;Guillemot & Hassan, 2017;Hobert, 2010;Huang et al, 2014;Johnson, 2020;Masoudi et al, 2021;Oproescu et al, 2021). Similar to signal-regulated TFs, important targets of proneural and spatial/lineage TFs are additional downstream TFs, including terminal selectors (Christensen et al, 2020;Masoudi et al, 2021).…”

“…Proneural TFs are necessary, and in some contexts sufficient, to induce neuronal fates (Figure 2) (Baker & Brown, 2018;Dennis et al, 2019;Guillemot & Hassan, 2017;Hobert, 2010;Huang et al, 2014;Johnson, 2020;Masoudi et al, 2021;Oproescu et al, 2021). Similar to signal-regulated TFs, important targets of proneural and spatial/lineage TFs are additional downstream TFs, including terminal selectors (Christensen et al, 2020;Masoudi et al, 2021). In addition, proneural TFs and some spatial/lineage TFs act as pioneer TFs modifying chromatin accessibility in a celltype specific manner that will determine the binding profiles of downstream expressed TFs (Aydin et al, 2019;Sen et al, 2019).…”

Open Frontiers in Neural Cell Type Investigations; Lessons From Caenorhabditis elegans and Beyond, Toward a Multimodal Integration

“…FOXD4/UNC-130 is expressed in and required for the diversification of different cell types (neurons AWA, ASG, ASI and glia ILsoD) arising from the same sublineage but not the diversification of similar types arising from other sub-lineages ( Sarafi-Reinach and Sengupta, 2000 ; Mizeracka et al, 2021 ). On the other hand, Atoh1/LIN-32 is expressed in and required for the specification of related, left/right or radially symmetrical, neural cell types generated from distinct sublineages ( Masoudi et al, 2021 ). The later transcription factor may control expression of terminal selectors in the specified cell types.…”

Cross-modality synthesis of EM time series and live fluorescence imaging

“…However, since neurons are typically identified in EM based on specialized adult morphologies it is challenging to identify them in the embryo during their emergence. It is primarily work using live FM that has examined the C. elegans nervous system during embryogenesis, providing insight into neurulation ( Shah et al, 2017b ; Barnes et al, 2020 ), organogenesis ( Low et al, 2019 ; Fan et al, 2019 ), neuropil formation ( Moyle et al, 2021 ; Rapti et al, 2017 ; Kennerdell et al, 2009 ; Shah et al, 2017a ; Sengupta et al, 2021 ), synaptic specificity ( Berghoff, 2021 ), as well as lineage differentiation and brain asymmetry ( Chuang et al, 2007 ; Cochella and Hobert, 2012 ; Masoudi et al, 2021 ). Lineage tracing in FM establishes definitive identities for cells via ancestry even when they lack distinctive positions or morphologies ( Shah et al, 2017a ; Bao et al, 2006 ) and light sheet microscopy allows imaging to extend into embryonic motion ( Wu et al, 2013 ).…”