Slit/Robo-mediated Axon Guidance in Tribolium and Drosophila: Divergent Genetic Programs Build Insect Nervous Systems

Dev Biol. 2012 Mar 1;363(1):266-78. doi: 10.1016/j.ydbio.2011.12.046. Epub 2012 Jan 8.

Abstract

As the complexity of animal nervous systems has increased during evolution, developmental control of neuronal connectivity has become increasingly refined. How has functional diversification within related axon guidance molecules contributed to the evolution of nervous systems? To address this question, we explore the evolution of functional diversity within the Roundabout (Robo) family of axon guidance receptors. In Drosophila, Robo and Robo2 promote midline repulsion, while Robo2 and Robo3 specify the position of longitudinal axon pathways. The Robo family has expanded by gene duplication in insects; robo2 and robo3 exist as distinct genes only within dipterans, while other insects, like the flour beetle Tribolium castaneum, retain an ancestral robo2/3 gene. Both Robos from Tribolium can mediate midline repulsion in Drosophila, but unlike the fly Robos cannot be down-regulated by Commissureless. The overall architecture and arrangement of longitudinal pathways are remarkably conserved in Tribolium, despite it having only two Robos. Loss of TcSlit causes midline collapse of axons in the beetle, a phenotype recapitulated by simultaneous knockdown of both Robos. Single gene knockdowns reveal that beetle Robos have specialized axon guidance functions: TcRobo is dedicated to midline repulsion, while TcRobo2/3 also regulates longitudinal pathway formation. TcRobo2/3 knockdown reproduces aspects of both Drosophila robo2 and robo3 mutants, suggesting that TcRobo2/3 has two functions that in Drosophila are divided between Robo2 and Robo3. The ability of Tribolium to organize longitudinal axons into three discrete medial-lateral zones with only two Robo receptors demonstrates that beetle and fly achieve equivalent developmental outcomes using divergent genetic programs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / metabolism*
  • Axons / physiology
  • Drosophila Proteins / classification
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Evolution, Molecular
  • Female
  • Gene Expression Regulation, Developmental
  • Genetic Variation
  • Immunohistochemistry
  • Insect Proteins / classification
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nervous System / embryology
  • Nervous System / metabolism
  • Phylogeny
  • RNA Interference
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction / genetics
  • Tribolium / embryology
  • Tribolium / genetics*
  • Tribolium / metabolism

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Robo2 protein, Drosophila
  • robo3 protein, Drosophila
  • roundabout protein
  • sli protein, Drosophila

Associated data

  • GENBANK/JN634958
  • GENBANK/JN634959