Relationships between protein isoforms and genetic functions demonstrate functional redundancy at the Broad-Complex during Drosophila metamorphosis

Dev Biol. 1997 Jul 15;187(2):267-82. doi: 10.1006/dbio.1997.8620.


Metamorphosis in holometabolous insects is an ecdysone-dependent process by which the larval form is replaced by a reproductive, adult form. At the onset of metamorphosis ecdysone induces a set of early genes which coordinate tissue-specific responses to hormone. The Broad-Complex (BR-C) early gene, which acts as a global regulator of tissue-specific responses to ecdysone, encodes a family of zinc-finger DNA binding proteins known as Z1, Z2, Z3, and Z4. Genetically the BR-C encodes three complementing functions, br, rbp, and 2Bc, and a class of npr1 alleles that fail to complement any of the other genetic functions. The effects of BR-C mutations on metamorphic development are highly pleiotropic, yet little is known about the roles of individual BR-C proteins in directing the required responses to ecdysone. Because the BR-C is a vital regulator of metamorphosis it is essential to establish the relationships between BR-C genetic functions and protein products. We present here the first general and definitive study of these relationships. Using heat-inducible transgenes we have rescued lethality associated with each of the complementing genetic functions and have restored transcriptional activity of tissue-specific BR-C(+)-dependent target genes. Our data lead us to conclude that br+ function is only provided by the Z2 isoform. We find that Z1 transgenes provide full rbp+ function, while Z4 provides partial function. Likewise, while Z3 provides full 2Bc+ function, Z2 also provides partial function. These results indicate possible functional redundancy or regulatory dependence (via autoregulation) associated with the rbp+ and 2Bc+ functions. The establishment of these relationships between BR-C genetic functions and protein isoforms is an important step toward understanding the roles of BR-C proteins in directing metamorphic responses to ecdysone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Dehydrogenase / biosynthesis
  • Alcohol Dehydrogenase / genetics
  • Animals
  • Animals, Genetically Modified
  • Central Nervous System / metabolism
  • Dopa Decarboxylase / biosynthesis
  • Dopa Decarboxylase / genetics
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila / growth & development
  • Drosophila Proteins*
  • Ecdysone / metabolism
  • Fat Body / metabolism
  • Gene Expression Regulation, Developmental*
  • Genes, Insect
  • Genes, Lethal
  • Genetic Complementation Test
  • Glue Proteins, Drosophila / biosynthesis
  • Glue Proteins, Drosophila / genetics
  • Male
  • Metamorphosis, Biological / genetics*
  • Mutation
  • Salivary Glands / metabolism
  • Transcription Factors / genetics*
  • Zinc Fingers / genetics*


  • Br protein, Drosophila
  • Drosophila Proteins
  • Glue Proteins, Drosophila
  • Transcription Factors
  • Ecdysone
  • Alcohol Dehydrogenase
  • Dopa Decarboxylase