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 language | English (US) |
|---|---|
| Pages (from-to) | e1008051 |
| Journal | PLoS genetics |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Molecular Biology
- Genetics
- Genetics(clinical)
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression
AU - Hartwell, Ryan D.
AU - England, Samantha J.
AU - Monk, Nicholas A.M.
AU - van Hateren, Nicholas J.
AU - Baxendale, Sarah
AU - Marzo, Mar
AU - Lewis, Katharine E
AU - Whitfield, Tanya T.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1008051
DO - 10.1371/journal.pgen.1008051
M3 - Article
VL - 15
SP - e1008051
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 4
ER -