PUBLICATION

Churchill regulates cell movement and mesoderm specification by repressing Nodal signaling

Authors

Londin, E.R., Mentzer, L., and Sirotkin, H.I.

ID

ZDB-PUB-071118-22

Date

2007

Source

BMC Developmental Biology 7(1): 120 (Journal)

Registered Authors

Sirotkin, Howard

Keywords

none

MeSH Terms

Nodal Protein
Animals
Trans-Activators/antagonists & inhibitors
Trans-Activators/genetics*
Transforming Growth Factor beta/antagonists & inhibitors*
Transforming Growth Factor beta/genetics
Cell Movement/genetics
Embryo, Nonmammalian
Zinc Fingers/genetics*
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish Proteins/antagonists & inhibitors
Zebrafish Proteins/genetics*
Signal Transduction
Mesoderm/embryology
Body Patterning/genetics

(all 16)

PubMed

17980025 Full text @ BMC Dev. Biol.

Abstract

BACKGROUND: Cell movements are essential to the determination of cell fates during development. The zinc-finger transcription factor, Churchill (ChCh) has been proposed to regulate cell fate by regulating cell movements during gastrulation in the chick. However, the mechanism of action of ChCh is not understood. RESULTS: We demonstrate that ChCh acts to repress the response to Nodal-related signals in zebrafish. When ChCh function is abrogated the expression of mesodermal markers is enhanced while ectodermal markers are expressed at decreased levels. In cell transplant assays, we observed that ChCh-deficient cells are more motile than wild-type cells. When placed in wild-type hosts, ChCh-deficient cells often leave the epiblast, migrate to the germ ring and are later found in mesodermal structures. We demonstrate that both movement of ChCh-compromised cells to the germ ring and acquisition of mesodermal character depend on the ability of the donor cells to respond to Nodal signals. Blocking Nodal signaling in the donor cells at the levels of Oep, Alk receptors or Fast1 inhibited migration to the germ ring and mesodermal fate change in the donor cells. We also detect additional unusual movements of transplanted ChCh-deficient cells which suggests that movement and acquisition of mesodermal character can be uncoupled. Finally, we demonstrate that ChCh is required to limit the transcriptional response to Nodal. CONCLUSIONS: These data establish a broad role for ChCh in regulating both cell movement and Nodal signaling during early zebrafish development. We show that chch is required to limit mesodermal gene expression, inhibit Nodal-dependant movement of presumptive ectodermal cells and repress the transcriptional response to Nodal signaling. These findings reveal a dynamic role for chch in regulating cell movement and fate during early development.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	control	Shield	presumptive mesoderm	RTPCR	Fig. 2
WT + MO1-churc1	standard conditions	Shield	presumptive mesoderm	RTPCR	Fig. 2
WT	control	90%-epiboly	ectoderm	RTPCR	Fig. 3
WT + MO1-churc1	standard conditions	90%-epiboly	ectoderm	RTPCR	Fig. 3
WT	control	90%-epiboly	ectoderm	RTPCR	Fig. 3
WT + MO1-churc1	standard conditions	90%-epiboly	ectoderm	RTPCR	Fig. 3
WT	control	90%-epiboly	endoderm	RTPCR	Fig. 3
WT + MO1-churc1	standard conditions	90%-epiboly	endoderm	RTPCR	Fig. 3
WT	control	90%-epiboly	mesoderm	RTPCR	Fig. 3
WT	control	Shield	presumptive mesoderm	RTPCR	Fig. 2

1 - 10 of 36

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-churc1	standard conditions	Prim-5	brain structure, abnormal	Fig. 1
WT + MO1-churc1	standard conditions	Prim-5	notochord deformed, abnormal	Fig. 1
WT + MO1-churc1	standard conditions	Prim-5	notochord increased width, abnormal	Fig. 1
WT + MO1-churc1	standard conditions	Prim-5	somite deformed, abnormal	Fig. 1
WT + MO1-churc1	standard conditions	Prim-5	somite increased size, abnormal	Fig. 1
WT + MO1-churc1	standard conditions	Prim-5	whole organism decreased length, abnormal	Fig. 1

1 - 6 of 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
tdgf1_unspecified		Unspecified	tdgf1

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
churc1	MO1-churc1	MRPHLNO

Fish

Fish
tdgf1^{unspecified/unspecified}
WT
WT + MO1-churc1

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Londin et al., 2007 ZDB-PUB-071118-22 PMID:17980025

Churchill regulates cell movement and mesoderm specification by repressing Nodal signaling

Londin et al., 2007

ZDB-PUB-071118-22
PMID:17980025