Abstract

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 4Drosophila 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.

Highlights

  • Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization

  • Panels a–c illustrate transgenic unpg-lacZ in control brains at embryonic stages E12, E14, and E16 showing progressive maturation of the deutocerebral– tritocerebral boundary (DTB) domain, enlarged in the Lower Right Inset of c. (d–f) Maintenance of DTB depends on FGF8 signaling: as illustrated by the successive developmental stages of htl-null mutant embryos, in which unpg and ems expression patterns are initially visible but those relating to the DTB are subsequently altered by embryonic stage 16. (Insets in c and f) Monochrome enlargements of the open boxed areas in a and f resolve rostrocaudal shortening in the mutant compared with the DTB of the wild type (Inset, c)

  • We have identified gene regulatory and character identity networks that underlie the formation of the deutocerebral– tritocerebral boundary in Drosophila

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Summary

Introduction

Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. Further cross-phyletic studies revealed correspondences in developmental genetic mechanisms underlying circuit formation and information processing of the vertebrate basal ganglia and the arthropod central complex, including pathologies [9, 21,22,23] These similarities extend to comparisons of the vertebrate hippocampus and the arthropod mushroom bodies, forebrain centers that support spatial navigation, allocentric memory, and associative learning [10, 24]. We describe conserved regulatory elements that mediate the spatiotemporal expression of developmental control genes directing the formation and function of midbrain circuits in flies, mice, and humans These circuits develop from corresponding midbrain-hindbrain boundary regions and regulate comparable behaviors for balance and motor control. Our findings suggest that conserved regulatory mechanisms specify cephalic circuits for sensory integration and coordinated behavior common to all animals that possess a brain

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