PUBLICATION

Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened

Authors

Ochi, H., Pearson, B.J., Chuang, P.T., Hammerschmidt, M., and Westerfield, M.

ID

ZDB-PUB-060616-49

Date

2006

Source

Developmental Biology 297(1): 127-140 (Journal)

Registered Authors

Hammerschmidt, Matthias, Ochi, Haruki, Pearson, Bret, Westerfield, Monte

Keywords

Clathrin, Endosomes, Hedgehog signaling, Patched, Skeletal muscle, Smoothened, Zebrafish

MeSH Terms

Cell Membrane/metabolism
Zebrafish/embryology*
Zebrafish/genetics
Membrane Proteins/genetics
Membrane Proteins/metabolism*
Drosophila Proteins/genetics
Drosophila Proteins/metabolism
Trans-Activators/genetics
Trans-Activators/metabolism*
Muscle Development*
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Receptors, Cell Surface/genetics
Receptors, Cell Surface/metabolism
Sequence Homology, Amino Acid
Muscles/cytology
Muscles/embryology
Protein Structure, Tertiary
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Animals
Receptors, G-Protein-Coupled/genetics
Receptors, G-Protein-Coupled/metabolism*
Hedgehog Proteins

(all 24)

PubMed

16765934 Full text @ Dev. Biol.

Abstract

Sharp borders between cells with different developmental fates are important for patterning of invertebrates, but are not well understood in vertebrates. Zebrafish slow muscle cells develop from adaxial cells, a one-cell-diameter-thick pseudo-epithelium immediately adjacent to the notochord. Hedgehog (Hh) signals from notochord specify adaxial cells to form slow muscle cells. Cells next to adaxial cells form fast muscle. This suggests that Hh signaling is locally regulated to produce a sharp border that separates slow and fast muscle precursors. To understand how Hh activity is locally regulated, we characterized the dynamic roles of Hhip, a protein that binds Hedgehog at the cell surface. Hhip is strongly expressed by adaxial cells and, together with Patched, the Hedgehog receptor, limits transduction of the Hedgehog signaling by Smoothened to adaxial cells. Hhip protein lacking its membrane associated domain still suppresses Hh activity but no longer acts synergistically with Patched. Hhip and Smoothened colocalize at the cell surface and, in response to Hedgehog, internalize together. Knockdown of Hhip blocks Smoothened internalization while increasing Hedgehog signaling and slow muscle formation. These data support a model in which Hhip regulates muscle development both by sequestering Hedgehog and by modulating localization of Smoothened.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
dmrt2a	AB	standard conditions	Bud	paraxial mesoderm	ISH	Fig. 2
dmrt2a	AB + MO2-hhip + MO3-hhip	standard conditions	Bud	paraxial mesoderm	ISH	Fig. 2
en1a	AB	standard conditions	Prim-5	muscle pioneer	ISH	Fig. S1
en1a	AB	standard conditions	Prim-5	muscle pioneer	ISH	Fig. 3
en1a	AB	standard conditions	Prim-5	muscle pioneer	ISH	Fig. 4
en1a	AB	standard conditions	Prim-5	muscle pioneer	ISH	Fig. S3
en1a	AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	muscle pioneer	ISH	Fig. S3
en1a	AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	muscle pioneer	ISH	Fig. 3
en1a	AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	muscle pioneer	ISH	Fig. 4
en1a	AB + MO1-ptch1 + MO1-ptch2 + MO2-hhip + MO3-hhip	standard conditions	Prim-5	muscle pioneer	ISH	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	fast muscle cell decreased amount, abnormal	Fig. 3
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	muscle pioneer increased amount, abnormal	Fig. 3
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	muscle pioneer increased amount, abnormal	Fig. 4
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	slow muscle cell increased amount, abnormal	Fig. 3
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	slow muscle cell increased amount, abnormal	Fig. 4
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	somite muscle pioneer increased amount, abnormal	Fig. 5
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	somite slow muscle cell increased amount, abnormal	Fig. 5
AB + MO1-ptch1 + MO1-ptch2	standard conditions	Prim-5	somite U-shaped, abnormal	Fig. 4
AB + MO1-ptch1 + MO1-ptch2 + MO2-hhip + MO3-hhip	standard conditions	Prim-5	muscle pioneer increased amount, abnormal	Fig. 3
AB + MO1-ptch1 + MO1-ptch2 + MO2-hhip + MO3-hhip	standard conditions	Prim-5	slow muscle cell increased amount, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
b577	Point Mutation	smo
b641	Point Mutation	smo
t4	Deficiency	shha
tc256d	Point Mutation	hhip
ty119	Point Mutation	gli2a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
hhip	MO2-hhip	MRPHLNO
hhip	MO3-hhip	MRPHLNO
ptch1	MO1-ptch1	MRPHLNO
ptch2	MO1-ptch2	MRPHLNO

Fish

Fish
AB
AB + MO1-ptch1 + MO1-ptch2
AB + MO1-ptch1 + MO1-ptch2 + MO2-hhip + MO3-hhip
AB + MO2-hhip + MO3-hhip
Df(Chr07)t4/t4
Df(Chr07)t4/t4 + MO2-hhip + MO3-hhip
gli2a^ty119/ty119
gli2a^ty119/ty119 + MO2-hhip + MO3-hhip
hhip^{tc256d/tc256d}
smo^b577/b577 (AB)

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Antibodies

Orthology

Gene	Orthology
hhip

Engineered Foreign Genes

Mapping

Ochi et al., 2006 ZDB-PUB-060616-49 PMID:16765934

Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened

Ochi et al., 2006

ZDB-PUB-060616-49
PMID:16765934