A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates

Hugo J. Parker, Bony De Kumar, Stephen A. Green, Karin D. Prummel, Christopher Hess, Charles K. Kaufman, Christian Mosimann, Leanne M. Wiedemann, Marianne E. Bronner () and Robb Krumlauf ()
Additional contact information
Hugo J. Parker: Stowers Institute for Medical Research
Bony De Kumar: Stowers Institute for Medical Research
Stephen A. Green: California Institute of Technology
Karin D. Prummel: University of Zurich
Christopher Hess: University of Zurich
Charles K. Kaufman: Washington University in Saint Louis
Christian Mosimann: University of Zurich
Leanne M. Wiedemann: Stowers Institute for Medical Research
Marianne E. Bronner: California Institute of Technology
Robb Krumlauf: Stowers Institute for Medical Research

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract In jawed vertebrates (gnathostomes), Hox genes play an important role in patterning head and jaw formation, but mechanisms coupling Hox genes to neural crest (NC) are unknown. Here we use cross-species regulatory comparisons between gnathostomes and lamprey, a jawless extant vertebrate, to investigate conserved ancestral mechanisms regulating Hox2 genes in NC. Gnathostome Hoxa2 and Hoxb2 NC enhancers mediate equivalent NC expression in lamprey and gnathostomes, revealing ancient conservation of Hox upstream regulatory components in NC. In characterizing a lamprey hoxα2 NC/hindbrain enhancer, we identify essential Meis, Pbx, and Hox binding sites that are functionally conserved within Hoxa2/Hoxb2 NC enhancers. This suggests that the lamprey hoxα2 enhancer retains ancestral activity and that Hoxa2/Hoxb2 NC enhancers are ancient paralogues, which diverged in hindbrain and NC activities. This identifies an ancestral mechanism for Hox2 NC regulation involving a Hox-TALE regulatory circuit, potentiated by inputs from Meis and Pbx proteins and Hox auto-/cross-regulatory interactions.

Date: 2019
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DOI: 10.1038/s41467-019-09197-8

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