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

Rhombencephalon/growth & development
Rhombencephalon/metabolism
Signal Transduction/genetics
Pre-B-Cell Leukemia Transcription Factor 1/genetics*
Homeodomain Proteins/genetics*
Animals
Embryo, Nonmammalian
In Situ Hybridization
Fibroblast Growth Factors/genetics*
Zebrafish/genetics
Zebrafish/growth & development
Embryonic Development/genetics
Zebrafish Proteins/genetics*
Gene Expression Regulation, Developmental/genetics
Neurons/metabolism
Body Patterning/genetics
Tretinoin/metabolism*

(all 17)

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

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
aldh1a2	AB	standard conditions	75%-epiboly	margin	ISH	Fig. 7
aldh1a2	AB	standard conditions	90%-epiboly	margin	ISH	Fig. 8
aldh1a2	AB + MO1-pbx2 + MO2-pbx2 + MO2-pbx4 + MO3-pbx4	standard conditions	90%-epiboly	margin	ISH	Fig. 8
aldh1a2	hoxb1a^{sa1191/sa1191}	standard conditions	75%-epiboly	margin	ISH	Fig. 7
aldh1a2	hoxb1a^{sa1191/sa1191}; hoxb1b^{ua1006/ua1006}	standard conditions	75%-epiboly	margin	ISH	Fig. 7
aldh1a2	hoxb1b^{ua1006/ua1006}	standard conditions	75%-epiboly	margin	ISH	Fig. 7
aldh1a2	pbx4^b557/b557	standard conditions	90%-epiboly	margin	ISH	Fig. 8
aldh1a2	pbx4^b557/b557 + MO1-pbx2 + MO2-pbx2 + MO2-pbx4 + MO3-pbx4	standard conditions	90%-epiboly	margin	ISH	Fig. 8
cyp26b1	AB	standard conditions	1-4 somites	presumptive rhombomere 3	ISH	Fig. 7
cyp26b1	AB	standard conditions	1-4 somites	presumptive rhombomere 4	ISH	Fig. 7

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: retinoic acid	1-4 somites	hindbrain neural plate hnf1ba expression increased amount, abnormal	Fig. 6
AB + MO1-pbx2 + MO2-pbx2 + MO2-pbx4 + MO3-pbx4	standard conditions	90%-epiboly	margin aldh1a2 expression decreased amount, abnormal	Fig. 8
hoxb1a^{sa1191/sa1191}	standard conditions	1-4 somites	midbrain hindbrain boundary neural keel fgf8a expression spatial pattern, abnormal	Fig. 9
hoxb1a^{sa1191/sa1191}	standard conditions	1-4 somites	midbrain hindbrain boundary neural keel morphology, abnormal	Fig. 9
hoxb1a^{sa1191/sa1191}	standard conditions	1-4 somites	presumptive rhombomere 2 fgf8a expression spatial pattern, abnormal	Fig. 9
hoxb1a^{sa1191/sa1191}	standard conditions	1-4 somites	presumptive rhombomere 3 cyp26b1 expression decreased amount, abnormal	Fig. 7
hoxb1a^{sa1191/sa1191}	standard conditions	5-9 somites	midbrain hindbrain boundary neural keel fgf8a expression spatial pattern, abnormal	Fig. S5
hoxb1a^{sa1191/sa1191}	standard conditions	10-13 somites	rhombomere 4 fgf3 expression decreased amount, abnormal	Fig. S4
hoxb1a^{sa1191/sa1191}	standard conditions	14-19 somites	rhombomere 4 hoxa2b expression decreased amount, abnormal	Fig. 2
hoxb1a^{sa1191/sa1191}	standard conditions	14-19 somites	rhombomere 4 hoxb1a expression decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b557		Point Mutation	pbx4
rw0Tg	Tg(isl1a:GFP)	Transgenic Insertion
sa1191		Point Mutation	hoxb1a
ua1006		Insertion	hoxb1b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
hoxb1b	TALEN1-hoxb1b	TALEN
pbx2	MO1-pbx2	MRPHLNO
pbx2	MO2-pbx2	MRPHLNO
pbx4	MO2-pbx4	MRPHLNO
pbx4	MO3-pbx4	MRPHLNO

Fish

Fish
AB
AB + MO1-pbx2 + MO2-pbx2 + MO2-pbx4 + MO3-pbx4
hoxb1a^{sa1191/sa1191}
hoxb1a^{sa1191/sa1191}; hoxb1b^{ua1006/ua1006}
hoxb1a^{sa1191/sa1191}; hoxb1b^{ua1006/ua1006}; rw0Tg
hoxb1a^{sa1191/sa1191}; rw0Tg
hoxb1b^{ua1006/ua1006}
hoxb1b^{ua1006/ua1006}; rw0Tg
pbx4^b557/b557
pbx4^b557/b557; hoxb1b^{ua1006/ua1006}

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-neurofilament-m	monoclonal			Mouse
Ab9-mapk	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Selland et al., 2018 ZDB-PUB-180303-2 PMID:29496480

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

Selland et al., 2018

ZDB-PUB-180303-2
PMID:29496480