TY - JOUR
T1 - A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates
AU - Parker, Hugo J.
AU - De Kumar, Bony
AU - Green, Stephen A.
AU - Prummel, Karin D.
AU - Hess, Christopher
AU - Kaufman, Charles K.
AU - Mosimann, Christian
AU - Wiedemann, Leanne M.
AU - Bronner, Marianne E.
AU - Krumlauf, Robb
N1 - Funding Information:
We thank Dorit Hockman, Tetsuto Miyashita, and Megan Martik for lamprey husbandry assistance, the Stowers Institute aquatics facility for zebrafish care, and Histology facility for sectioning assistance. This study was conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH and protocols approved by the Institutional Animal Care and Use Committees of the Stowers Institute (Zebrafish, RK Protocol: #2015-0149), California Institute of Technology (lamprey, MEB Protocol: #1436-11), and the veterinary office of UZH and the Canton of Zürich. K.D.P., C.H., and C.M. were supported by Science Foundation (SNSF) professorship (C.M. grant 170623), a Marie Curie Career Integration Grant from the European Commission (C.M. grant PCIG14-GA-2013-631984), the Swiss Cancer League, and the Canton of Zürich. H.J.P., B.D.K., L.M.W., and R.K. were supported by the Stowers Institute (R.K. grant #2013-1001). S.A.G. and M.E.B. were supported by grants R01NS086907 and R01DE017911.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062820544&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-09197-8
DO - 10.1038/s41467-019-09197-8
M3 - Article
C2 - 30867425
AN - SCOPUS:85062820544
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1189
ER -