PUBLICATION

Coordinate regulation of retinoic acid synthesis by pbx genes and fibroblast growth factor signaling by hoxb1b is required for hindbrain patterning and development

Authors
Selland, L.G., Koch, S., Laraque, M., Waskiewicz, A.J.
ID
ZDB-PUB-180303-2
Date
2018
Source
Mechanisms of Development   150: 28-41 (Journal)
Registered Authors
Waskiewicz, Andrew
Keywords
FGF, Hoxb1b, RA, hoxb1, hoxb1a, pbx4
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Embryo, Nonmammalian
  • Embryonic Development/genetics
  • Fibroblast Growth Factors/genetics*
  • Gene Expression Regulation, Developmental/genetics
  • Homeodomain Proteins/genetics*
  • In Situ Hybridization
  • Neurons/metabolism
  • Pre-B-Cell Leukemia Transcription Factor 1/genetics*
  • Rhombencephalon/growth & development
  • Rhombencephalon/metabolism
  • Signal Transduction/genetics
  • Tretinoin/metabolism*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
PubMed
29496480 Full text @ Mech. Dev.
Abstract
The vertebrate hindbrain is composed of a series of lineage-restricted segments termed rhombomeres. Segment-specific gene expression drives unique programs of neuronal differentiation. Two critical embryonic signaling pathways, Fibroblast Growth Factor (FGF) and Retinoic Acid (RA), regulate early embryonic rhombomere patterning. The earliest expressed hox genes, hoxb1b and hoxb1a in zebrafish, are logical candidates for establishing signaling networks that specify segmental identity. We sought to determine the mechanism by which hox genes regulate hindbrain patterning in zebrafish. We demonstrate that hoxb1a regulates r4-specific patterning, while hoxb1b regulates rhombomere segmentation and size. Hoxb1a and hoxb1b redundantly regulate vhnf1 expression. Loss of hoxb1b together with pbx4 reverts the hindbrain to a groundstate identity, demonstrating the importance of hox genes in patterning nearly the entire hindbrain, and a key requirement for Pbx in this process. Additionally, we provide evidence that while pbx genes regulate RA signaling, hoxb1b regulates hindbrain identity through complex regulation of FGF signaling.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping