Drosophila mef2 expression during mesoderm development is controlled by a complex array of cis-acting regulatory modules

Hanh T. Nguyen, Xiaolei H Xu

Research output: Contribution to journalArticle

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Abstract

The function of the Drosophila mef2 gene, a member of the MADS box supergene family of transcription factors, is critical for terminal differentiation of the three major muscle cell types, namely somatic, visceral, and cardiac. During embryogenesis, mef2 undergoes multiple phases of expression, which are characterized by initial broad mesodermal expression, followed by restricted expression in the dorsal mesoderm, specific expression in muscle progenitors, and sustained expression in the differentiated musculatures. In this study, evidence is presented that temporally and spatially specific mef2 expression is controlled by a complex array of cis-acting regulatory modules that are responsive to different genetic signals. Functional testing of ~12 kb of 5' flanking region of the mef2 gene showed that the initial widespread mesodermal expression is achieved through a 280-bp twist-dependent enhancer. The subsequent dorsal mesoderm-restricted mef2 expression is mediated through a 460-bp dpp- responsive regulatory module, which involves the function of the Smad4 homolog Medea and contains several binding sites for Medea and Mad. The analysis also showed that regulated mef2 expression in the caudal and trunk visceral mesoderm, which give rise to longitudinal and circular gut musculatures, respectively, is under the control of distinct enhancer elements. In addition, mef2 expression in the cardioblasts of the heart is dependent upon at least two distinct enhancers, which are active at different periods during embryogenesis. Moreover, multiple regulatory elements are differentially activated for specific expression in presumptive muscle founders, prefusion myoblasts, and differentiated muscle fibers. Taken together, the presented data suggest that specific expression of the mef2 gene in myogenic lineages in the Drosophila embryo is the result of multiple genetic inputs that act in an additive manner upon distinct enhancers in the 5' flanking region.

Original languageEnglish (US)
Pages (from-to)550-566
Number of pages17
JournalDevelopmental Biology
Volume204
Issue number2
DOIs
StatePublished - Dec 15 1998
Externally publishedYes

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Keywords

  • Dpp
  • Drosophila mef2
  • Medea
  • Mesoderm development
  • Myogenesis
  • Twist

ASJC Scopus subject areas

  • Developmental Biology

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