The role of transcription bodies in gene expression: what embryos teach us

Martino Ugolini  ¹ , Nadine L Vastenhouw  ¹

Affiliations

• PMID: 39912709
• DOI: 10.1042/BST20240599

Abstract

Transcription does not occur diffusely throughout the nucleus but is concentrated in specific areas. Areas of accumulated transcriptional machinery have been called clusters, hubs, or condensates, while transcriptionally active areas have been referred to as transcription factories or transcription bodies. Despite the widespread occurrence of transcription bodies, it has been difficult to study their assembly, function, and effect on gene expression. This review highlights the advantages of developmental model systems such as zebrafish and fruit fly embryos, in addressing these questions. We focus on three important discoveries that were made in embryos. (i) It had previously been suggested that, in transcription bodies, the different steps of the transcription process are organized in space. We explore how work in embryos has revealed that they can also be organized in time. In this case, transcription bodies mature from transcription factor clusters to elongating transcription bodies. This type of organization has important implications for transcription body function. (ii) The relevance of clustering for in vivo gene regulation has benefited greatly from studies in embryos. We discuss examples in which transcription bodies regulate developmental gene expression by compensating for low transcription factor concentrations and low-affinity enhancers. Finally, (iii) while accumulations of transcriptional machinery can facilitate transcription locally, work in embryos showed that transcription bodies can also sequester the transcriptional machinery, modulating the availability for activity at other sites. In brief, the reviewed literature highlights the properties of developmental model organisms that make them powerful systems for uncovering the form and function of transcription bodies.

Keywords: Developmental model systems; Gene regulation; Nuclear organization; Sequestration; Transcription bodies.

Transcriptomic neuron types vary topographically in function and morphology

Inbal Shainer ^{#  1   2} , Johannes M Kappel ^{#  1   3} , Eva Laurell  ¹ , Joseph C Donovan  ¹ , Martin W Schneider  ¹ , Enrico Kuehn  ¹ , Irene Arnold-Ammer  ¹ , Manuel Stemmer  ¹ , Johannes Larsch  ^{1   4} , Herwig Baier  ⁵

Affiliations

• PMID: 39939759
• PMCID: PMC11864986
• DOI: 10.1038/s41586-024-08518-2

Abstract

Neuronal phenotypic traits such as morphology, connectivity and function are dictated, to a large extent, by a specific combination of differentially expressed genes. Clusters of neurons in transcriptomic space correspond to distinct cell types and in some cases-for example, Caenorhabditis elegans neurons¹ and retinal ganglion cells^2-4-have been shown to share morphology and function. The zebrafish optic tectum is composed of a spatial array of neurons that transforms visual inputs into motor outputs. Although the visuotopic map is continuous, subregions of the tectum are functionally specialized^5,6. Here, to uncover the cell-type architecture of the tectum, we transcriptionally profiled its neurons, revealing more than 60 cell types that are organized in distinct anatomical layers. We measured the visual responses of thousands of tectal neurons by two-photon calcium imaging and matched them with their transcriptional profiles. Furthermore, we characterized the morphologies of transcriptionally identified neurons using specific transgenic lines. Notably, we found that neurons that are transcriptionally similar can diverge in shape, connectivity and visual responses. Incorporating the spatial coordinates of neurons within the tectal volume revealed functionally and morphologically defined anatomical subclusters within individual transcriptomic clusters. Our findings demonstrate that extrinsic, position-dependent factors expand the phenotypic repertoire of genetically similar neurons.