Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates

Jessika C. Bridi, Zoe N. Ludlow, Benjamin Kottler, Beate Hartmann, Lies Vanden Broeck, Jonah Dearlove, Markus Göker, Nicholas J. Strausfeld, Patrick Callaerts, Frank Hirth

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. However, the underlying mechanisms have remained elusive. Here, we identify a gene regulatory and character identity network defining the deutocerebral-tritocerebral boundary (DTB) in Drosophila. This network comprises genes homologous to those directing midbrain-hindbrain boundary (MHB) formation in vertebrates and their closest chordate relatives. Genetic tracing reveals that the embryonic DTB gives rise to adult midbrain circuits that in flies control auditory and vestibular information processing and motor coordination, as do MHB-derived circuits in vertebrates. DTB-specific gene expression and function are directed by cis-regulatory elements of developmental control genes that include homologs of mammalian Zinc finger of the cerebellum and Purkinje cell protein 4. Drosophila DTB-specific cis-regulatory elements correspond to regulatory sequences of human ENGRAILED-2, PAX-2, and DACHSHUND-1 that direct MHB-specific expression in the embryonic mouse brain. We show that cis-regulatory elements and the gene networks they regulate direct the formation and function of midbrain circuits for balance and motor coordination in insects and mammals. Regulatory mechanisms mediating the genetic specification of cephalic neural circuits in arthropods correspond to those in chordates, thereby implying their origin before the divergence of deuterostomes and ecdysozoans.

Original languageEnglish (US)
Pages (from-to)19544-19555
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number32
StatePublished - Aug 11 2020


  • Brain
  • Evolution
  • Gene regulatory network
  • Homology
  • Neural circuit

ASJC Scopus subject areas

  • General


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