PUBLICATION

Hand2 Regulates Extracellular Matrix Remodeling Essential for Gut-Looping Morphogenesis in Zebrafish

Authors

Yin, C., Kikuchi, K., Hochgreb, T., Poss, K.D., and Stainier, D.Y.

ID

ZDB-PUB-100719-51

Date

2010

Source

Developmental Cell 18(6): 973-984 (Journal)

Registered Authors

Hochgreb, Tatiana, Kikuchi, Kazu, Poss, Kenneth D., Stainier, Didier, Yin, Chunyue

Keywords

none

MeSH Terms

Cell Movement/physiology
Extracellular Matrix/metabolism*
Organogenesis/physiology*
Matrix Metalloproteinases/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Body Patterning/physiology
Mesoderm/cytology
Mesoderm/metabolism
Zebrafish/embryology*
Animals
Transgenes/genetics
Basic Helix-Loop-Helix Transcription Factors/genetics
Basic Helix-Loop-Helix Transcription Factors/metabolism*
Cell Differentiation/physiology
Cell Lineage/physiology
Animals, Genetically Modified
Gastrointestinal Tract/cytology
Gastrointestinal Tract/embryology*
Gastrointestinal Tract/metabolism*
Laminin/metabolism
Green Fluorescent Proteins/genetics
Green Fluorescent Proteins/metabolism

(all 23)

PubMed

20627079 Full text @ Dev. Cell

Abstract

Extracellular matrix (ECM) remodeling is critical for organogenesis, yet its molecular regulation is poorly understood. In zebrafish, asymmetric migration of the epithelial lateral plate mesoderm (LPM) displaces the gut leftward, allowing correct placement of the liver and pancreas. To observe LPM migration at cellular resolution, we transgenically expressed EGFP under the control of the regulatory sequences of the bHLH transcription factor gene hand2. We found that laminin is distributed along the LPM/gut boundary during gut looping, and that it appears to become diminished by the migrating hand2-expressing cells. Laminin diminishment is necessary for LPM migration and is dependent on matrix metalloproteinase (MMP) activity. Loss of Hand2 function causes reduced MMP activity and prolonged laminin deposition at the LPM/gut boundary, leading to failed asymmetric LPM migration and gut looping. Our study reveals an unexpected role for Hand2, a key regulator of cell specification and differentiation, in modulating ECM remodeling during organogenesis.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp2b	WT	standard conditions	Prim-5	lateral plate mesoderm	ISH	Fig. 2
chrd	WT	standard conditions	Prim-5	somite ventral region	ISH	Fig. 2
EGFP	fr13Tg; pd24Tg	heat shock	Prim-15	mesoderm lateral region	IHC	Fig. 2
EGFP	hand2^c99/c99; pd24Tg	standard conditions	Prim-5	lateral plate mesoderm	IHC	Fig. 3
EGFP	hand2^c99/c99; pd24Tg	standard conditions	Prim-5	lateral plate mesoderm	IHC	Fig. 4
EGFP	hand2^c99/c99; pd24Tg	standard conditions	Prim-15	mesoderm lateral region	IHC	Fig. 4
EGFP	hand2^c99/c99; pd24Tg	standard conditions	Prim-15	mesoderm lateral region	IHC	Fig. 3
EGFP	pd24Tg	standard conditions	Prim-5	lateral plate mesoderm	IHC	Fig. 1
EGFP	pd24Tg	standard conditions	Prim-5	lateral plate mesoderm	IHC	Fig. 2
EGFP	pd24Tg	standard conditions	Prim-5	lateral plate mesoderm	IHC	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: pharmaceutical	Prim-15	determination of intestine left/right asymmetry process quality, normal	Fig. 5
fr13Tg; pd24Tg	heat shock	Prim-15	determination of intestine left/right asymmetry disrupted, abnormal	Fig. 2
hand2^c99/+	control	Prim-15	determination of intestine left/right asymmetry process quality, normal	Fig. 5
hand2^c99/+	chemical treatment: pharmaceutical	Prim-15	determination of intestine left/right asymmetry disrupted, abnormal	Fig. 5
hand2^c99/+ + MO4-mmp14a	standard conditions	Prim-15	determination of intestine left/right asymmetry disrupted, abnormal	Fig. 7
hand2^c99/c99	standard conditions	Prim-15	determination of intestine left/right asymmetry disrupted, abnormal	Fig. 3
hand2^c99/c99	standard conditions	Prim-15	digestive tract development disrupted, abnormal	Fig. 3
hand2^c99/c99	standard conditions	Prim-15	mesodermal cell migration disrupted, abnormal	Fig. 3
hand2^c99/c99	standard conditions	Long-pec	liver duplicated, abnormal	Fig. 3
hand2^c99/c99	standard conditions	Long-pec	pancreas duplicated, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
c99		Insertion	hand2
fr13Tg	Tg(hsp70l:bmp2b)	Transgenic Insertion
pd24Tg	TgBAC(hand2:EGFP)	Transgenic Insertion
s40		Unknown	hand2
s804		Point Mutation	lamb1a
w30Tg	Tg(hsp70l:dnXla.Bmpr1a-GFP)	Transgenic Insertion

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
mmp14a	MO4-mmp14a	MRPHLNO
spaw	MO1-spaw	MRPHLNO

Fish

Fish
fr13Tg
fr13Tg; pd24Tg
hand2^c99/c99
hand2^c99/c99; pd24Tg
hand2^c99/+
hand2^c99/+
hand2^c99/+ + MO4-mmp14a
hand2^s40/s40
hand2^s40/s40; pd24Tg
lamb1a^s804/s804

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Yin et al., 2010 ZDB-PUB-100719-51 PMID:20627079

Hand2 Regulates Extracellular Matrix Remodeling Essential for Gut-Looping Morphogenesis in Zebrafish

Yin et al., 2010

ZDB-PUB-100719-51
PMID:20627079