RT Journal Article
SR Electronic
T1 Ancestral Regulatory Mechanisms Specify Conserved Midbrain Circuitry in Arthropods and Vertebrates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 820555
DO 10.1101/820555
A1 Jessika C. Bridi
A1 Zoe N. Ludlow
A1 Benjamin Kottler
A1 Beate Hartmann
A1 Lies Vanden Broeck
A1 Jonah Dearlove
A1 Markus Göker
A1 Nicholas J. Strausfeld
A1 Patrick Callaerts
A1 Frank Hirth
YR 2019
UL http://biorxiv.org/content/early/2019/10/28/820555.abstract
AB 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. We show 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 is directed by cis-regulatory elements (CREs) of developmental control genes that include homologs of mammalian Zinc finger of the cerebellum and Purkinje cell protein 4. Moreover, Drosophila DTB-specific CREs correspond to regulatory sequences of human ENGRAILED-2, PAX-2 and DACHSHUND-1 that direct MHB-specific expression in the embryonic mouse brain. Together, these findings imply ancestral regulatory mechanisms mediating the genetic specification of midbrain-cerebellar circuitry for balance and motor control that may predated the radiation of cephalic nervous systems across the animal kingdom.