Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression

Ryan D. Hartwell, Samantha J. England, Nicholas A.M. Monk, Nicholas J. van Hateren, Sarah Baxendale, Mar Marzo, Katharine E Lewis, Tanya T. Whitfield

Research output: Contribution to journalArticle

Abstract

In the zebrafish, Fgf and Hh signalling assign anterior and posterior identity, respectively, to the poles of the developing ear. Mis-expression of fgf3 or inhibition of Hh signalling results in double-anterior ears, including ectopic expression of hmx3a. To understand how this double-anterior pattern is established, we characterised transcriptional responses in Fgf gain-of-signalling or Hh loss-of-signalling backgrounds. Mis-expression of fgf3 resulted in rapid expansion of anterior otic markers, refining over time to give the duplicated pattern. Response to Hh inhibition was very different: initial anteroposterior asymmetry was retained, with de novo duplicate expression domains appearing later. We show that Hmx3a is required for normal anterior otic patterning, and that otic patterning defects in hmx3a-/- mutants are a close phenocopy to those seen in fgf3-/- mutants. However, neither loss nor gain of hmx3a function was sufficient to generate full ear duplications. Using our data to infer a transcriptional regulatory network required for acquisition of otic anterior identity, we can recapitulate both the wild-type and the double-anterior pattern in a mathematical model.

Original languageEnglish (US)
Pages (from-to)e1008051
JournalPLoS genetics
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Zebrafish
Danio rerio
Ear
ears
defect
asymmetry
mutants
Gene Regulatory Networks
refining
regulation
Theoretical Models
mathematical models
loss
mutant

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Hartwell, R. D., England, S. J., Monk, N. A. M., van Hateren, N. J., Baxendale, S., Marzo, M., ... Whitfield, T. T. (2019). Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression. PLoS genetics, 15(4), e1008051. https://doi.org/10.1371/journal.pgen.1008051

Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression. / Hartwell, Ryan D.; England, Samantha J.; Monk, Nicholas A.M.; van Hateren, Nicholas J.; Baxendale, Sarah; Marzo, Mar; Lewis, Katharine E; Whitfield, Tanya T.

In: PLoS genetics, Vol. 15, No. 4, 01.04.2019, p. e1008051.

Research output: Contribution to journalArticle

Hartwell, RD, England, SJ, Monk, NAM, van Hateren, NJ, Baxendale, S, Marzo, M, Lewis, KE & Whitfield, TT 2019, 'Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression', PLoS genetics, vol. 15, no. 4, pp. e1008051. https://doi.org/10.1371/journal.pgen.1008051
Hartwell RD, England SJ, Monk NAM, van Hateren NJ, Baxendale S, Marzo M et al. Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression. PLoS genetics. 2019 Apr 1;15(4):e1008051. https://doi.org/10.1371/journal.pgen.1008051
Hartwell, Ryan D. ; England, Samantha J. ; Monk, Nicholas A.M. ; van Hateren, Nicholas J. ; Baxendale, Sarah ; Marzo, Mar ; Lewis, Katharine E ; Whitfield, Tanya T. / Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression. In: PLoS genetics. 2019 ; Vol. 15, No. 4. pp. e1008051.
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