PUBLICATION

Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation

Authors

Drerup, C.M., Wiora, H.M., Topczewski, J., and Morris, J.A.

ID

ZDB-PUB-090706-20

Date

2009

Source

Development (Cambridge, England) 136(15): 2623-2632 (Journal)

Registered Authors

Drerup, Katie (Catherine), Topczewski, Jacek

Keywords

foxd3, sox10, disc1, Disrupted In Schizophrenia 1, Zebrafish, Cranial neural crest, Neural crest migration, Schizophrenia

MeSH Terms

Skull/cytology
Skull/metabolism
Time Factors
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Zebrafish/embryology*
Zebrafish/genetics
Neural Crest/cytology*
Neural Crest/drug effects
Cell Differentiation*/drug effects
Apoptosis/drug effects
Biomarkers/metabolism
Sequence Homology, Amino Acid
Cell Movement*/drug effects
SOXE Transcription Factors/genetics*
SOXE Transcription Factors/metabolism
Gene Expression Regulation, Developmental/drug effects
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism*
Forkhead Transcription Factors/genetics*
Forkhead Transcription Factors/metabolism
RNA Splice Sites
Oligonucleotides, Antisense/pharmacology
Animals
Craniofacial Abnormalities/genetics
Craniofacial Abnormalities/pathology
Cell Proliferation/drug effects
Neuroglia/cytology
Neuroglia/metabolism
Gene Knockdown Techniques

(all 30)

PubMed

19570850 Full text @ Development

Abstract

This work reports the characterization and functional analysis of disrupted in schizophrenia 1 (disc1), a well-documented schizophrenia-susceptibility gene, in zebrafish cranial neural crest (CNC). Our data demonstrated that disc1 was expressed in zebrafish CNC cells. Loss of Disc1 resulted in persistent CNC cell medial migration, dorsal to the developing neural epithelium, and hindered migration away from the region dorsal to the neural rod. General CNC cell motility was not affected by Disc1 knockdown, however, as the speed of CNC cells was indistinguishable from that of wild-type counterparts. We determined that the failure of CNC cells to migrate away from the neural rod correlated with the enhanced expression of two transcription factors, foxd3 and sox10. These transcription factors have many functions in CNC cells, including the maintenance of precursor pools, timing of migration onset, and the induction of cell differentiation. Our work, in conjunction with previous studies, suggests that the perpetuation of expression of these factors affects several aspects of CNC cell development, leading to a loss of craniofacial cartilage and an expansion of peripheral cranial glia. Based on our data, we propose a model in which Disc1 functions in the transcriptional repression of foxd3 and sox10, thus mediating CNC cell migration and differentiation.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
disc1	ba2Tg/+	standard conditions	14-19 somites	cranial neural crest	ISH	Fig. 1
disc1	WT	standard conditions	Protruding-mouth	cranial cartilage	ISH	Fig. 1
disc1	WT	standard conditions	10-13 somites	cranial neural crest	ISH	Fig. 1
disc1	WT	standard conditions	14-19 somites	cranial neural crest	ISH	Fig. 1
disc1	WT	standard conditions	Prim-5	neural crest	ISH	Fig. 1
disc1	WT	standard conditions	Prim-5	notochord	ISH	Fig. 1
disc1	WT	standard conditions	Prim-5	trunk neural crest	ISH	Fig. 1
EGFP	ba2Tg/+	standard conditions	14-19 somites	cranial neural crest	IHC	Fig. 1
EGFP	ba2Tg/+	control	5-9 somites to 10-13 somites	cranial neural crest	IHC	Fig. 4
EGFP	ba2Tg/+	control	10-13 somites to 20-25 somites	cranial neural crest	IHC	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO3-disc1	standard conditions	10-13 somites	cranial neural crest increased size, abnormal	Fig. 3
WT + MO3-disc1	standard conditions	10-13 somites	neural crest cell migration disrupted, abnormal	Fig. 3
WT + MO3-disc1	standard conditions	Long-pec	posterior lateral line ganglion glial cell increased amount, abnormal	Fig. 8
WT + MO3-disc1	standard conditions	Long-pec	trigeminal ganglion glial cell increased amount, abnormal	Fig. 8
WT + MO3-disc1	standard conditions	Day 5	cranial cartilage malformed, abnormal	Fig. 2
WT + MO4-disc1	standard conditions	10-13 somites	cranial neural crest increased size, abnormal	Fig. 3
WT + MO4-disc1	standard conditions	10-13 somites	neural crest cell migration disrupted, abnormal	Fig. 3
WT + MO4-disc1	standard conditions	Day 5	cranial cartilage malformed, abnormal	Fig. 2
ba2Tg/+ + MO3-disc1	standard conditions	5-9 somites to 10-13 somites	neural crest cell migration disrupted, abnormal	Fig. 4
ba2Tg/+ + MO3-disc1	standard conditions	10-13 somites to 20-25 somites	neural crest cell migration disrupted, abnormal	Fig. 5

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ba2Tg	Tg(-4.9sox10:EGFP)	Transgenic Insertion
m241		Unknown	sox10

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
disc1	MO3-disc1	MRPHLNO
disc1	MO4-disc1	MRPHLNO
sox10	MO1-sox10	MRPHLNO
sox10	MO3-sox10	MRPHLNO

Fish

Fish
ba2Tg/+
ba2Tg/+ + MO3-disc1
sox10^m241/+
sox10^m241/+ + MO3-disc1
WT
WT + MO3-disc1
WT + MO3-disc1 + MO3-sox10
WT + MO3-sox10
WT + MO4-disc1

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Drerup et al., 2009 ZDB-PUB-090706-20 PMID:19570850

Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation

Drerup et al., 2009

ZDB-PUB-090706-20
PMID:19570850