Control of Organogenesis by Hox Genes

Hombría, James Castelli-Gair; Sánchez-Higueras, Carlos; Sánchez‐Herrero, Ernesto

doi:10.1007/978-3-319-42767-6_12

Cited by 6 publications

(3 citation statements)

References 266 publications

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“…The Hox proteins belong to the conserved class of HD TFs ( 23 ). They are expressed along the longitudinal axis in cnidarians ( 24 ) and bilaterians ( 25 ), and orchestrate the development and homeostasis of a diversity of cell and tissue types ( 25 , 26 ). Understanding their molecular function has been a central aim in Developmental Biology.…”

Section: Introductionmentioning

confidence: 99%

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

Carnesecchi

Boumpas

Sanchez

et al. 2021

Nucleic Acids Research

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Transcription factors (TFs) play a pivotal role in cell fate decision by coordinating gene expression programs. Although most TFs act at the DNA layer, few TFs bind RNA and modulate splicing. Yet, the mechanistic cues underlying TFs activity in splicing remain elusive. Focusing on the Drosophila Hox TF Ultrabithorax (Ubx), our work shed light on a novel layer of Ubx function at the RNA level. Transcriptome and genome-wide binding profiles in embryonic mesoderm and Drosophila cells indicate that Ubx regulates mRNA expression and splicing to promote distinct outcomes in defined cellular contexts. Our results demonstrate a new RNA-binding ability of Ubx. We find that the N51 amino acid of the DNA-binding Homeodomain is non-essential for RNA interaction in vitro, but is required for RNA interaction in vivo and Ubx splicing activity. Moreover, mutation of the N51 amino acid weakens the interaction between Ubx and active RNA Polymerase II (Pol II). Our results reveal that Ubx regulates elongation-coupled splicing, which could be coordinated by a dynamic interplay with active Pol II on chromatin. Overall, our work uncovered a novel role of the Hox TFs at the mRNA regulatory layer. This could be an essential function for other classes of TFs to control cell diversity.

show abstract

Section: Introductionmentioning

confidence: 99%

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

Carnesecchi

Boumpas

Sanchez

et al. 2021

Nucleic Acids Research

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show abstract

“…Cells, both individually and collectively, act in concert with the extracellular matrix (ECM) to self-assemble organs and organ systems ( Devine et al, 2005 ; Loganathan et al, 2016c ; Serna-Morales et al, 2023 ; Walma and Yamada, 2020 ). Shaped by gene regulatory networks and signaling events, transcriptomes drive the transformation of cells into organs ( Bhattaram et al, 2010 ; Castelli-Gair Hombria et al, 2016 ; Dassaye et al, 2016 ; Huilgol et al, 2019 ; Selleri et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Organogenetic transcriptomes of the Drosophila embryo at single cell resolution

Peng,

Jackson,

Palicha

et al. 2024

Development

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To gain insight into the transcription programs activated during the formation of Drosophila larval structures, we carried out single cell RNA sequencing during two periods of Drosophila embryogenesis: stages 10 – 12, when most organs are first specified and initiate morphological and physiological specialization, and stages 13 – 16, when organs achieve their final mature architectures and begin to function. Our data confirm previous findings with regards to functional specialization of some organs – the salivary gland and trachea – and clarify the embryonic functions of another – the plasmatocytes. We also identify two early developmental trajectories in germ cells and uncover a potential role for proteolysis during germline stem cell specialization. We identify the likely cell type of origin for key components of the Drosophila matrisome and several commonly used Drosophila embryonic cell culture lines. Finally, we compare our findings to other recent related studies and to other modalities for identifying tissue-specific gene expression patterns. These data provide a useful community resource for identifying many new players in tissue-specific morphogenesis and functional specialization of developing organs.

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“…The Hox proteins belong to the conserved class of HD TFs (Bürglin and Affolter, 2016). They are expressed along the longitudinal axis in cnidarians (He et al, 2018) and bilaterians (Pearson et al, 2005), and orchestrate the development and homeostasis of a diversity of cell and tissue types (Castelli-Gair Hombría et al, 2016; Pearson et al, 2005). Understanding their molecular function has been a central aim in Developmental Biology.…”

Section: Introductionmentioning

confidence: 99%

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

Carnesecchi

Boumpas

et al. 2021

Preprint

View full text Add to dashboard Cite

Transcription Factors (TFs) play a pivotal role in cell fate decision by coordinating distinct gene expression programs. Although most TFs act at the DNA regulatory layer, few TFs can bind RNA and modulate mRNA splicing. Yet, the mechanistic cues underlying TFs function in splicing remain elusive. Focusing on the Drosophila Hox TF Ultrabithorax (Ubx), our work shed light on a novel layer of Ubx function at the RNA level. Transcriptome and genome-wide binding profiles in embryonic mesoderm and Drosophila cells indicate that Ubx regulates mRNA expression and splicing to promote distinct functions in defined cellular contexts. Ubx modulates splicing via its DNA-binding domain, the Homeodomain (HD). Our results demonstrate a new RNA-binding ability of Ubx in cells and in vitro. Notably, the N51 amino acid of the HD, which mediates Ubx-DNA interaction, is non-essential for Ubx-RNA interaction in vitro but is required in vivo. We find that the N51 amino acid is necessary to mediate interaction between Ubx and the active form of the RNA Polymerase II (Pol II S2Phos) in Drosophila cells. By combining molecular and imaging approaches, our results reveal that Ubx mediates elongation-coupled splicing via a dynamic interplay with active Pol II and chromatin binding. Overall, our work uncovered a novel role of the Hox TFs at the mRNA regulatory layer. This could be an essential function for other classes of TFs to control cell diversity.

show abstract

Control of Organogenesis by Hox Genes

Cited by 6 publications

References 266 publications

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

Organogenetic transcriptomes of the Drosophila embryo at single cell resolution

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

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