Distinct functions of acj6 splice forms in odor receptor gene choice

J Neurosci. 2010 Apr 7;30(14):5028-36. doi: 10.1523/JNEUROSCI.6292-09.2010.

Abstract

Individual olfactory receptor neurons (ORNs) selectively express one or a small number of odor receptors from among a large receptor repertoire. The expression of an odor receptor dictates the odor response spectrum of the ORN. The process of receptor gene choice relies in part on a combinatorial code of transcription factors. In Drosophila, the POU domain transcription factor Acj6 is one element of the transcription factor code. In acj6 null mutants, many ORNs do not express an appropriate odor receptor gene and thus are not correctly specified. We find that acj6 is alternatively spliced to yield many structurally distinct transcripts in the olfactory organs. We generate flies that express single splice forms of acj6 in an acj6(-) background. We find that different splice forms are functionally distinct; they differ in their abilities to specify ORN identities. Some individual splice forms can fully rescue the specification of some ORNs. Individual splice forms can function both positively and negatively in receptor gene regulation. ORNs differ in their requirements for splice forms; some are not fully rescued by any single splice form tested, suggesting that some ORNs may require the combinatorial action of multiple splice forms. Late expression of some acj6 splice forms is sufficient to rescue some ORN classes, consistent with a direct role for Acj6 isoforms in receptor gene expression. The results indicate that alternative splicing may add another level of richness to the regulatory code that underlies the process of odor receptor gene choice.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Alternative Splicing / physiology
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / genetics
  • Gene Knockout Techniques
  • Larva / genetics
  • Larva / physiology
  • Molecular Sequence Data
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Olfactory Receptor Neurons / physiology*
  • POU Domain Factors / deficiency
  • POU Domain Factors / genetics*
  • POU Domain Factors / physiology
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics*
  • Protein Isoforms / physiology
  • Receptors, Odorant / biosynthesis
  • Receptors, Odorant / deficiency
  • Receptors, Odorant / genetics*

Substances

  • Drosophila Proteins
  • Nerve Tissue Proteins
  • POU Domain Factors
  • Protein Isoforms
  • Receptors, Odorant
  • acj6 protein, Drosophila