PUBLICATION

Zebrafish Cdx4 regulates neural crest cell specification and migratory behaviors in the posterior body

Authors

Rocha, M., Kushkowski, E., Schnirman, R., Booth, C., Singh, N., Beadell, A., Prince, V.E.

ID

ZDB-PUB-210815-1

Date

2021

Source

Developmental Biology 480: 25-38 (Journal)

Registered Authors

Kushkowski, Elaine, Prince, Victoria E., Rocha, Manuel

Keywords

Cdx4, Foxd3, Neural crest, Tailbud, Zebrafish

MeSH Terms

Transcription Factors/genetics*
Transcription Factors/metabolism
Animals
Neural Crest/metabolism*
Zebrafish Proteins/metabolism
Morphogenesis/genetics
Cell Movement/genetics
Forkhead Transcription Factors/metabolism
Zebrafish/genetics
Zebrafish/metabolism
Gene Expression Regulation, Developmental/genetics
Neural Tube/metabolism
Gene Expression/genetics
Body Patterning/genetics
Neurulation/genetics
Homeodomain Proteins/genetics*
Homeodomain Proteins/metabolism
Cell Differentiation/genetics
Neural Plate/metabolism

(all 19)

PubMed

34389276 Full text @ Dev. Biol.

Abstract

The neural crest (NC) is a transient multipotent cell population that migrates extensively to produce a remarkable array of vertebrate cell types. NC cell specification progresses in an anterior to posterior fashion, resulting in distinct, axial-restricted subpopulations. The anterior-most, cranial, population of NC is specified as gastrulation concludes and neurulation begins, while more posterior populations become specified as the body elongates. The mechanisms that govern development of the more posterior NC cells remain incompletely understood. Here, we report a key role for zebrafish Cdx4, a homeodomain transcription factor, in the development of posterior NC cells. We demonstrate that cdx4 is expressed in trunk NC cell progenitors, directly binds NC cell-specific enhancers in the NC GRN, and regulates expression of the key NC development gene foxd3 in the posterior body. Moreover, cdx4 mutants show disruptions to the segmental pattern of trunk NC cell migration due to loss of normal leader/follower cell dynamics. Finally, using cell transplantation to generate chimeric specimens, we show that Cdx4 does not function in the paraxial mesoderm-the environment adjacent to which crest migrates-to influence migratory behaviors. We conclude that cdx4 plays a critical, and likely tissue autonomous, role in the establishment of trunk NC migratory behaviors. Together, our results indicate that cdx4 functions as an early NC specifier gene in the posterior body of zebrafish embryos.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cdx4	WT	standard conditions	5-9 somites	neural crest cell	ISH	Fig. 1
cdx4	WT	standard conditions	10-13 somites	neural crest cell	ISH	Fig. 1
cdx4	WT	standard conditions	10-13 somites	somite lateral region	ISH	Fig. 1
cdx4	WT	standard conditions	10-13 somites	somite 3	ISH	Fig. 1
cdx4	WT	standard conditions	5-9 somites	tail bud	ISH	Fig. 1
foxd3	cdx4^ch107/ch107	standard conditions	10-13 somites	neural tube dorsal region	ISH	Fig. 3
foxd3	cdx4^ch107/ch107	standard conditions	10-13 somites	tail bud	ISH	Fig. 3
foxd3	WT	standard conditions	5-9 somites	neural crest cell	ISH	Fig. 1
foxd3	WT	standard conditions	10-13 somites	premigratory neural crest	ISH	Fig. 1
foxd3	WT	standard conditions	10-13 somites	somite posterior region	ISH	Fig. 1

1 - 10 of 13

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
cdx4^ch107/+	standard conditions	Bud	neural plate border transcription coregulator binding process quality, normal	Fig. 2
cdx4^ch107/+	standard conditions	Bud	premigratory neural crest transcription coregulator binding process quality, normal	Fig. 2
cdx4^ch107/+	standard conditions	5-9 somites	neural plate border transcription coregulator binding process quality, normal	Fig. 2
cdx4^ch107/+	standard conditions	5-9 somites	premigratory neural crest transcription coregulator binding process quality, normal	Fig. 2
cdx4^ch107/ch107	standard conditions	10-13 somites	neural tube dorsal region foxd3 expression decreased amount, abnormal	Fig. 3
cdx4^ch107/ch107	standard conditions	10-13 somites	tail bud foxd3 expression decreased amount, abnormal	Fig. 3
cdx4^ch107/ch107	standard conditions	Prim-5	migratory trunk neural crest neural crest cell migration decreased process quality, abnormal	Fig. 4
cdx4^ch107/ch107	standard conditions	Prim-5	trunk neural crest cell ab3-sox10 labeling spatial pattern, abnormal	Fig. 4
cdx4^ch107/ch107; vu234Tg/vu234Tg	standard conditions	Prim-5	neural crest cell migration onset quality, abnormal	Fig. 5
cdx4^ch107/ch107; vu234Tg/vu234Tg	standard conditions	Prim-5	trunk neural crest cell mRFP expression spatial pattern, abnormal	Fig. 5

1 - 10 of 10

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ch107		Indel	cdx4
ka6Tg	Tg(2.3gfap:GFP)	Transgenic Insertion
kca66Tg	Tg(h2az2a:h2az2a-GFP)	Transgenic Insertion
vu234Tg	Tg(sox10:mRFP)	Transgenic Insertion

1 - 4 of 4

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdx4	CRISPR1-cdx4	CRISPR

Fish

Fish
cdx4^ch107/ch107
cdx4^ch107/ch107; vu234Tg/vu234Tg
cdx4^ch107/+
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab3-sox10	polyclonal	sox10	IgG	Rabbit
Ab-A4.1025	monoclonal		IgG2a	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP
mRFP	EFG	mRFP

Mapping

Rocha et al., 2021 ZDB-PUB-210815-1 PMID:34389276

Zebrafish Cdx4 regulates neural crest cell specification and migratory behaviors in the posterior body

Rocha et al., 2021

ZDB-PUB-210815-1
PMID:34389276