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Hmx gene conservation identifies the origin of vertebrate cranial ganglia

Papdogiannis, Vasileios and Pennati, Alessandro and Parker, Hugo J. and Rothbächer, Ute and Patthey, Cedric and Bronner, Marianne E. and Shimeld, Sebastian M. (2022) Hmx gene conservation identifies the origin of vertebrate cranial ganglia. Nature, 605 (7911). pp. 701-705. ISSN 0028-0836. doi:10.1038/s41586-022-04742-w.

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The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia, whose neurons arise predominantly from cranial placodes; however, the understanding of the evolutionary origin of placodes and cranial sensory ganglia is hampered by the anatomical differences between living lineages and the difficulty in assigning homology between cell types and structures. Here we show that the homeobox transcription factor Hmx is a constitutive component of vertebrate sensory ganglion development and that in the tunicate Ciona intestinalis, Hmx is necessary and sufficient to drive the differentiation programme of bipolar tail neurons, cells previously thought to be homologues of neural crest. Using Ciona and lamprey transgenesis, we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx expression in the stem-vertebrate lineage. We also show notably robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and point to bipolar tail neurons as homologues of cranial sensory ganglia.

Item Type:Article
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URLURL TypeDescription
n ReadCube access Paper ItemData ItemData ItemData ItemStowers Original Data Repository
Pennati, Alessandro0000-0002-2766-2966
Parker, Hugo J.0000-0001-7646-2007
Rothbächer, Ute0000-0002-9989-6139
Patthey, Cedric0000-0002-2627-9578
Bronner, Marianne E.0000-0003-4274-1862
Shimeld, Sebastian M.0000-0003-0195-7536
Alternate Title:Hmx gene conservation identifies the evolutionary origin of vertebrate cranial ganglia
Additional Information:© 2022 Nature Publishing Group. Received 14 November 2019; Accepted 07 April 2022; Published 18 May 2022. We thank A. Stolfi and R. Zeller for sharing plasmids used in the Ciona CRISPR and overexpression studies, respectively; H. Escriva for hosting C.P. and for access to his amphioxus facility; and S. Green for lamprey husbandry assistance. V.P. was supported by a Natural Motion scholarship. V.P. and S.M.S. acknowledge the Elizabeth Hannah Jenkinson fund for financial support. V.P. also thanks T. Manousaki and C. Tsigenopoulos for their support while based in HCMR. A.P. was supported by the Accademia Nazionale dei Lincei while working in Oxford and by the H2020 Marie Sklodowska-Curie COFUND ARDRE to U.R. while working in Innsbruck. C.P. was supported by an EMBO Long Term Fellowship while working in Oxford. M.E.B. acknowledges support from award R35NS111564 from the NIH. H.J.P. was supported by funds from the Stowers Institute (grant no. 1001). Data availability: Cloned Hmx gene sequences have been deposited in Genbank accessions MN264670–MN264672. RNA-seq data have been deposited in SRA accession GSE141046. Original data underlying Fig. 4b, c of this manuscript can be accessed from the Stowers Original Data Repository at Contributions: V.P., C.P and S.M.S. conceived the study. V.P. conducted lamprey gene expression analysis, CNE identification, analysis of lamprey reporter gene experiments, Ciona Hmx expression analysis, Ciona Hmx overexpression analysis and RNA-seq and the molecular phylogenetic analyses. A.P. conducted Ciona CNE identification and reporter gene experiments, tests of lamprey CNE activity in Ciona, CRISPR and overexpression reporter analyses, and analysis of Ciona Hmx and Ngn gene expression. C.P. conducted the amphioxus in situ hybridization and participated in RNA-seq data analysis. H.J.P. conducted the lamprey reporter construct injections and analysis. U.R., M.E.B. and S.M.S. supervised the work. All authors contributing to drafting and editing the manuscript. The authors declare no competing interests. Peer review information: Nature thanks Noriyuki Satoh and the other, anonymous reviewers for their contribution to the peer review of this work.
Funding AgencyGrant Number
Natural Motion ScholarshipUNSPECIFIED
Elizabeth Hannah Jenkinson FundUNSPECIFIED
Accademia Nazionale dei LinceiUNSPECIFIED
Marie Curie FellowshipUNSPECIFIED
European Molecular Biology Organization (EMBO)UNSPECIFIED
Stowers Institute1001
Subject Keywords:Embryology; Evolutionary developmental biology
Issue or Number:7911
Record Number:CaltechAUTHORS:20200909-144305477
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Official Citation:Papadogiannis, V., Pennati, A., Parker, H.J. et al. Hmx gene conservation identifies the origin of vertebrate cranial ganglia. Nature 605, 701–705 (2022).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105301
Deposited By: Tony Diaz
Deposited On:09 Sep 2020 21:55
Last Modified:07 Jun 2022 22:14

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