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Background <p>The development of functional muscles in <i>Drosophila melanogaster</i> relies on precise spatial and temporal transcriptional control, orchestrated by complex gene regulatory networks. Central to this regulation are cis-regulatory modules (CRMs), which integrate inputs from transcription factors to fine-tune gene expression during myogenesis. In this study, we investigate the transcriptional regulation of the LIM-homeodomain transcription factor Tup (Tailup/Islet-1), a key regulator of dorsal muscle development.</p> Methods <p>Using a combination of CRISPR-Cas9-mediated deletion and transcriptional analyses, we examined the role of multiple CRMs in regulating <i>tup</i> expression.</p> Results <p>We demonstrate that <i>tup</i> expression is controlled by multiple CRMs that function redundantly to maintain robust <i>tup</i> transcription in dorsal muscles. These mesodermal <i>tup</i> CRMs act sequentially and differentially during the development of dorsal muscles and other tissues, including heart cells and alary muscles. We show that activity of the two late-acting CRMs govern late-phase <i>tup</i> expression through positive autoregulation, whereas an early enhancer initiates transcription independently. Deletion of both late-acting CRMs results in muscle identity shifts and defective muscle patterning. Detailed morphological analyses reveal muscle misalignments at intersegmental borders.</p> Conclusions <p>Our findings underscore the importance of CRM-mediated autoregulation and redundancy in ensuring robust and precise <i>tup</i> expression during muscle development. These results provide insights into how multiple CRMs coordinate gene regulation to ensure proper muscle identity and function.</p>

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Multiple cis-regulatory modules ensure robust tup/islet1 function in dorsal muscle identity specification

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月25日

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  • Aurore Pelletier,
  • Alexandre Carayon,
  • Yannick Carrier,
  • Coralie Sengenès,
  • Laurence Dubois,
  • Jean-Louis Frendo

摘要

Background

The development of functional muscles in Drosophila melanogaster relies on precise spatial and temporal transcriptional control, orchestrated by complex gene regulatory networks. Central to this regulation are cis-regulatory modules (CRMs), which integrate inputs from transcription factors to fine-tune gene expression during myogenesis. In this study, we investigate the transcriptional regulation of the LIM-homeodomain transcription factor Tup (Tailup/Islet-1), a key regulator of dorsal muscle development.

Methods

Using a combination of CRISPR-Cas9-mediated deletion and transcriptional analyses, we examined the role of multiple CRMs in regulating tup expression.

Results

We demonstrate that tup expression is controlled by multiple CRMs that function redundantly to maintain robust tup transcription in dorsal muscles. These mesodermal tup CRMs act sequentially and differentially during the development of dorsal muscles and other tissues, including heart cells and alary muscles. We show that activity of the two late-acting CRMs govern late-phase tup expression through positive autoregulation, whereas an early enhancer initiates transcription independently. Deletion of both late-acting CRMs results in muscle identity shifts and defective muscle patterning. Detailed morphological analyses reveal muscle misalignments at intersegmental borders.

Conclusions

Our findings underscore the importance of CRM-mediated autoregulation and redundancy in ensuring robust and precise tup expression during muscle development. These results provide insights into how multiple CRMs coordinate gene regulation to ensure proper muscle identity and function.