PUBLICATION

Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish

Authors

Farooq, M., Sulochana, K.N., Pan, X., To, J., Sheng, D., Gong, Z., and Ge, R.

ID

ZDB-PUB-080331-6

Date

2008

Source

Developmental Biology 317(1): 336-353 (Journal)

Registered Authors

Gong, Zhiyuan, Pan, Xiufang

Keywords

Histone deacetylase, Liver, Pancreas, Organogenesis, Zebrafish, VPA

MeSH Terms

Embryo, Nonmammalian/metabolism
Histone Deacetylases/metabolism*
Organogenesis*
Zebrafish Proteins/metabolism
Liver/embryology*
Pancreas, Exocrine/embryology
Animals
Zebrafish/embryology*
Zebrafish/metabolism
Growth Differentiation Factors

(all 10)

PubMed

18367159 Full text @ Dev. Biol.

Abstract

Histone deacetylases (HDACs) are key transcription regulators that function by deacetylating histones/transcription factors and modifying chromatin structure. In this work, we showed that chemical inhibition of HDACs by valproic acid (VPA) led to impaired liver development in zebrafish mainly by inhibiting specification, budding, and differentiation. Formation of exocrine pancreas but not endocrine pancreas was also inhibited. The liver defects induced by VPA correlate with suppressed total HDAC enzymatic activity, but are independent of angiogenesis inhibition. Gene knockdown by morpholino demonstrated that hdac3 is specifically required for liver formation while hdac1 is more globally required for multiple development processes in zebrafish including liver/exocrine pancreas formation. Furthermore, overexpression onockdown by morpholino demonstrated that hdac3 is specifically required for liver formation while hdac1 is more globally required for multiple develof hdac3 but not hdac1 partially rescued VPA induced small liver. One mechanism by which hdac3 regulates zebrafish liver growth is through inhibiting growth differentiation factor 11 (gdf11), a unique target of hdac3 and a member of the transforming growth factor beta family. Simultaneous overexpression or morpholino knockdown showed that hdac3 and gdf11 function antagonistically in zebrafish liver development. These results revealed a novel and specific role of hdac3 in liver development and the distinct functions between hdac1 and hdac3 in zebrafish embryonic development.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cp	WT	control	Protruding-mouth	liver	ISH	Fig. 7
cp	WT	control	Long-pec	liver	ISH	Fig. 1
cp	WT	control	Day 5	liver	ISH	Fig. 7
cp	WT	control	Protruding-mouth	liver	ISH	Fig. 1
cp	WT	chemical treatment: sodium valproate	Day 4	liver	ISH	Fig. 1
cp	WT	control	Prim-15	liver	ISH	Fig. 1
cp	WT	control	Prim-15	liver	ISH	Fig. 7
cp	WT	control	Day 4	liver	ISH	Fig. 1
cp	WT	control	Day 5	liver	ISH	Fig. 1
cp	WT	control	Long-pec	liver	ISH	Fig. 7

1 - 10 of 220

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-gdf11	standard conditions	Day 5	exocrine pancreas increased size, abnormal	Fig. 12
WT + MO1-hdac1	standard conditions	Day 5	exocrine pancreas development paedomorphic growth, abnormal	Fig. 6
WT + MO1-hdac3	standard conditions	Prim-15	liver decreased size, abnormal	Fig. 8
WT + MO1-hdac3	standard conditions	Prim-15	liver development paedomorphic growth, abnormal	Fig. 8
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	cranial cartilage aplastic, abnormal	Fig. 6
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	eye decreased size, abnormal	Fig. 6
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	head decreased size, abnormal	Fig. 6
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	heart edematous, abnormal	Fig. 6
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	liver decreased size, abnormal	Fig. 9
gz15Tg + MO1-hdac1	standard conditions	Protruding-mouth	liver development paedomorphic growth, abnormal	Fig. 9

1 - 10 of 19

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
gz15Tg	Tg(ela3l:EGFP) Tg(fabp10a:DsRed)	Transgenic Insertion
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
gdf11	MO1-gdf11	MRPHLNO
hdac1	MO1-hdac1	MRPHLNO
hdac3	MO1-hdac3	MRPHLNO
hdac3	MO2-hdac3	MRPHLNO
vegfaa	MO1-vegfaa	MRPHLNO

Fish

Fish
gz15Tg
gz15Tg + MO1-gdf11
gz15Tg + MO1-gdf11 + MO1-hdac3
gz15Tg + MO1-hdac1
gz15Tg + MO1-hdac1 + MO1-hdac3
gz15Tg + MO1-hdac3
gz15Tg; y1Tg
WT
WT + MO1-gdf11
WT + MO1-hdac1

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
EGFP	EFG	EGFP
RFP	EFG	RFP

Mapping

Farooq et al., 2008 ZDB-PUB-080331-6 PMID:18367159

Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish

Farooq et al., 2008

ZDB-PUB-080331-6
PMID:18367159