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The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

ABSTRACT: During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state, with several transcription factors following a broad-to-restricted expression dynamic as development proceeds, supporting neuron subtype identities. The relevance of this temporal refinement remains however unclear, these broad-to-restricted transcription factors being selectively involved in neurons in which they are ultimately maintained. Here we found that Dach1 encodes for a bona fide broad-to-restricted transcription factor retained and required in tactile somatosensory neurons. Within developing nociceptors, we demonstrate that Prdm12 contributes to Dach1 extinction. Using genetic approaches to prevent its temporal restriction during somatosensory development, we reveal that Dach1 refinement is a prerequisite for the appropriate transcriptional maturation of somatosensory subtypes from which it becomes ultimately excluded. These findings highlight the essential role played by Dach1 during somatosensory neuron development. They further demonstrate that the broad-to-restricted temporal pattern followed by several transcription factors is physiologically relevant to achieve appropriate transcriptional maturation of somatosensory neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE270844 | GEO | 2025/02/26

REPOSITORIES: GEO

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The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

Project description:During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state, with several transcription factors following a broad-to-restricted expression dynamic as development proceeds, supporting neuron subtype identities. The relevance of this temporal refinement remains however unclear, these broad-to-restricted transcription factors being selectively involved in neurons in which they are ultimately maintained. Here we found that Dach1 encodes for a bona fide broad-to-restricted transcription factor retained and required in tactile somatosensory neurons. Within developing nociceptors, we demonstrate that Prdm12 contributes to Dach1 extinction. Using genetic approaches to prevent its temporal restriction during somatosensory development, we reveal that Dach1 refinement is a prerequisite for the appropriate transcriptional maturation of somatosensory subtypes from which it becomes ultimately excluded. These findings highlight the essential role played by Dach1 during somatosensory neuron development. They further demonstrate that the broad-to-restricted temporal pattern followed by several transcription factors is physiologically relevant to achieve appropriate transcriptional maturation of somatosensory neurons.

2025-02-26 | GSE270845 | GEO

The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

Project description:The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

| PRJNA1128622 | ENA

The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

Project description:The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

| PRJNA1128621 | ENA

The emergence of transcriptional identity in somatosensory neurons

Project description:Primary somatosensory neurons are diverse neurons that report salient features of our internal and external environments. How specialized gene expression programs emerge during development to endow each somatosensory neuron subtype with unique properties is unclear. To analyze the developmental progression of transcriptional maturation of each principal somatosensory neuron subtype, we generated a transcriptomic atlas of cells traversing the somatosensory lineage. We find that somatosensory neurogenesis leads to neurons in a transcriptionally unspecialized state, characterized by trace expression of subtype-specific genes yet co-expression of transcription factors (TFs) that become restricted to select subtypes as development proceeds. Single cell transcriptomic analysis using sensory neurons from mutant mice lacking representative broad-to-restricted TFs revealed that they are essential for establishing subtype specific gene programs in subtypes where their expression is maintained, while leaving other subtypes unaffected. We also identify a role for neuronal targets by demonstrating that nerve growth factor influences subtype-restricted patterns of TFs. Our findings support a model in which extrinsic cues orchestrate somatosensory neuron diversification by influencing the expression pattern of TFs that promote transcriptional specialization of somatosensory neuron subtypes.

2019-10-19 | GSE139088 | GEO

Whole transcriptome analysis of FACS purified somatosensory neuron subtypes and whole dorsal root ganglia tissue

Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets. SNS-Cre mice were bred with Rosa26-TdTomato mice to generate SNS-Cre/TdTomato reporter mice. Parv-Cre mice were bred with Rosa26-TdTomato mice to generate Parv-Cre/TdTomato mice. Isolectin B4-FITC was used to stain the surface of SNS-Cre/TdTomato reporter mice. We used these strategies of fluorescent labeling to purify distinct murine sensory neuron subsets from the dorsal root ganglia (DRG) by fluorescence activated cell sorting (FACS). Neurons were sorted directly in Qiazol for total RNA extraction and microarray analysis. Whole DRG tissue was also included for transcriptome analysis to compare with purified neuronal populations.

2014-12-23 | E-GEOD-55114 | biostudies-arrayexpress

Transcription profiling timecourse of induced DACH1 expression in a human breast cancer cell line

Project description:The vertebrate homologues of Drosophila dachsund, DACH1 and DACH2, have been implicated as important regulatory genes in development. DACH1 plays a role in retinal and pituitary precursor cell proliferation and DACH2 plays a specific role in myogenesis. DACH proteins contain a domain (DS-domain) that is conserved with the proto-oncogenes Ski and Sno. Since the Ski/Sno proto-oncogenes repress AP-1 and SMAD signaling, we hypothesized that DACH1 might play a similar cellular function. Herein, DACH1 was found to be expressed in breast cancer cell lines and to inhibit TGF-beta induced apoptosis. DACH1 repressed TGF-beta induction of AP-1 and Smad signaling in gene reporter assays and repressed endogenous TGF-beta responsive genes by microarray analyses. DACH1 bound to endogenous NCoR and Smad4 in cultured cells and DACH1 co-localized with NCoR in nuclear dot-like structures. NCoR enhanced DACH1 repression and the repression of TGF-beta-induced AP-1 or Smad-signaling by DACH1 required the DACH1 DS domain. The DS-domain of DACH was sufficient for NCoR-binding at a Smad4-binding site. Smad4 was required for DACH1 repression of Smad signaling. In Smad4 null HTB-134 cells, DACH1 inhibited the activation of SBE-4 reporter activity induced by Smad2 or Smad3 only in the presence of Smad4. DACH1 participates in the negative regulation of TGF-beta signaling by interacting with NCoR and Smad4.

2007-07-19 | E-GEOD-685 | biostudies-arrayexpress

Whole transcriptome analysis of FACS purified somatosensory neuron subtypes and whole dorsal root ganglia tissue

2014-12-23 | GSE55114 | GEO

Single-Cell Transcriptomic Analysis of Somatosensory Neurons Uncovers Temporal Development of Neuropathic Pain

Project description:Single-Cell Transcriptomic Analysis of Somatosensory Neurons Uncovers Temporal Development of Neuropathic Pain

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DACH1 expression in U87 cells

Project description:Loss or reduction in function of tumor suppressor genes contributes to tumorigenesis. We identified a novel homozygous deletion of DACH1 in gliomas. We generated U87TR-Da glioma cell line, where DACH1 expression could be activated by exposure of cells to doxycycline, and examined changing global gene expression by DACH1 expression. Expression of DACH1 in U87TR-Da cells can be induced by exposure of the cells to doxycycline. We analyzed gene expression profiles of DACH1-induced/repressed U87TR-Da cells. And we also compared gene expression profiles of DACH1-induced/repressed U87TR-Da cells under different culture condition, DMEMF(serum-containing) and NBE(serum-free)

2011-07-19 | E-GEOD-19678 | biostudies-arrayexpress

Dach1 downregulation marks a lymphoid-primed progenitor in early haematopoiesis (2X96 cells)

Project description:A classical view of blood cell development is that multipotent haematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. The Lin–c-kit+Sca1+Flt3+ stage, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Through single cell RNA-sequencing, we identify heterogeneous expression of Dach1 and associated genes in this fraction where it co-expressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1-GFP reporter mice, we identify a transcriptionally and functionally unique Dach1– subpopulation within LMPPs with lymphoid potential but devoid of myeloid potential. We term these ‘lymphoid-primed progenitors’, or LPPs. These findings define the earliest branch point of lymphoid development in haematopoiesis and a means for their prospective isolation.

2019-08-27 | GSE136341 | GEO

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