Robust regulatory architecture of pan-neuronal gene expression

Leyva-Díaz, Eduardo; Hobert, Oliver

doi:10.1016/j.cub.2022.02.040

Cited by 32 publications

(31 citation statements)

References 61 publications

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“…Fosmids are generally 30-50 kb genomic fragments, usually containing several genes up/downstream of a gene of interest and can be expected to include all cisregulatory information of a tagged locus. Indeed, the expression pattern of many fosmid reporters is successfully recapitulated by CRISPR/Cas9 genome-engineered reporter alleles [7,[16][17][18]. A recently published nervous system wide scRNA transcriptome atlas, called CeN-GEN [19] is also largely congruent with an atlas of homeodomain expression profiles that was based on either fosmid-based reporters or CRISPR/Cas9-engineered reporter alleles [6].…”

Section: Reporter Alleles Refine Some Homeodomain Protein Expression ...mentioning

confidence: 99%

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

et al. 2022

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Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 14 homeobox genes in 24 distinct neuron classes that are mostly unrelated by location, function and lineage history. 12 of these 24 neuron classes had no homeobox gene function ascribed to them before, while in the other 12 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analyses, 113 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.

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Section: Reporter Alleles Refine Some Homeodomain Protein Expression ...mentioning

confidence: 99%

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

et al. 2022

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“…Furthermore, although unc-33::gfp expression is unaltered in unc-3 mutants, unc-119::gfp and unc-44::SL2::NLS::mKate2 reporters show a slight defect (n > 3 experiments; Figure S6D ). Thus, UNC-3 may promote cytoskeletal gene expression in the PDA neuron, but this effect would be partially redundant with the activities of other transcriptional regulators (e.g., Stefanakis et al, 2015 ; Leyva-Díaz and Hobert, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

A developmental pathway for epithelial-to-motoneuron transformation in C. elegans

Rashid

Tevlin

et al. 2022

Cell Reports

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“…Loss of NFYA-1 does not eliminate pan-neuronal gene expression (Figure 4 and S4). A previous study similarly showed that six members of the CUT homeodomain TF family are redundantly required to partially control pan-neuronal gene expression (Leyva-Diaz and Hobert, 2022). We hypothesized that NFYA-1 controls pan-neuronal gene expression either by directly regulating CUT gene expression or by cooperating with CUT TFs at panneuronal gene loci.…”

Section: Nfya-1 Cooperates With Multiple Tfs To Regulate Pan-neuronal...mentioning

confidence: 91%

Nuclear Factor-Y is a Pervasive Regulator of Neuronal Gene Expression

Moreira

Papatheodorou

Deng

et al. 2023

Preprint

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Nervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the Nuclear Factor Y (NF-Y) TF as a pervasive regulator of both neuron-type-specific and pan-neuronal gene expression. Mapping global NF-Y targets reveals direct binding to the cis-regulatory regions of pan-neuronal genes and terminal selector TFs. We show that NFYA-1 controls pan-neuronal gene expression directly through binding to CCAAT boxes in target gene promoters and indirectly by regulating the expression of terminal selector TFs. Further, we find that NFYA-1 regulation of neuronal gene expression is important for neuronal activity and motor function. Thus, our research sheds light on how global neuronal gene expression programs are buffered through direct and indirect regulatory mechanisms.

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Robust regulatory architecture of pan-neuronal gene expression

Cited by 32 publications

References 61 publications

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

A developmental pathway for epithelial-to-motoneuron transformation in C. elegans

Nuclear Factor-Y is a Pervasive Regulator of Neuronal Gene Expression

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