PUBLICATION

Pax2a, Sp5a and Sp5l act downstream of Fgf and Wnt to coordinate sensory-neural patterning in the inner ear

Authors
Tan, A.L., Mohanty, S., Guo, J., Lekven, A.C., Riley, B.B.
ID
ZDB-PUB-221018-88
Date
2022
Source
Developmental Biology   492: 139-153 (Journal)
Registered Authors
Lekven, Arne, Riley, Bruce
Keywords
CRISPR/Cas9, Hair cells, Statoacoustic ganglion, atoh1a, neurog1
MeSH Terms
  • Animals
  • Ear, Inner*/metabolism
  • Fibroblast Growth Factors/metabolism
  • Gene Expression Regulation, Developmental
  • PAX2 Transcription Factor/genetics
  • PAX2 Transcription Factor/metabolism
  • Wnt Signaling Pathway
  • Zebrafish*/genetics
  • Zebrafish Proteins/genetics
PubMed
36244503 Full text @ Dev. Biol.
Abstract
In zebrafish, sensory epithelia and neuroblasts of the inner ear form simultaneously in abutting medial and lateral domains, respectively, in the floor of the otic vesicle. Previous studies support regulatory roles for Fgf and Wnt, but how signaling is coordinated is poorly understood. We investigated this problem using pharmacological and transgenic methods to alter Fgf or Wnt signaling from early placodal stages to evaluate later changes in growth and patterning. Blocking Fgf at any stage reduces proliferation of otic tissue and terminates both sensory and neural specification. Wnt promotes proliferation in the otic vesicle but is not required for sensory or neural development. However, sustained overactivation of Wnt laterally expands sensory epithelia and blocks neurogenesis. pax2a, sp5a and sp5l are coregulated by Fgf and Wnt and show overlapping expression in the otic placode and vesicle. Gain- and loss-of-function studies show that these genes are together required for Wnt's suppression of neurogenesis, as well as some aspects of sensory development. Thus, pax2a, sp5a and sp5l are critical for mediating Fgf and Wnt signaling to promote spatially localized sensory and neural development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping