PUBLICATION

Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b

Authors

Ye, D., Wang, X., Wei, C., He, M., Wang, H., Wang, Y., Zhu, Z., Sun, Y.

ID

ZDB-PUB-190924-12

Date

2019

Source

PLoS Genetics 15: e1008306 (Journal)

Registered Authors

He, Mudan, Sun, Yonghua, Wei, Changyong, Ye, Ding, Zhu, Zuoyan

Keywords

none

MeSH Terms

Zebrafish/metabolism
Zebrafish/physiology*
Transforming Growth Factor beta/metabolism
Animals
Intracellular Signaling Peptides and Proteins/metabolism*
Body Patterning/physiology
HSP70 Heat-Shock Proteins/metabolism
Embryonic Development/genetics
Embryonic Development/physiology
Female
Zebrafish Proteins/metabolism*
Signal Transduction
Embryo, Nonmammalian/metabolism
Bone Morphogenetic Protein 2/metabolism*
Secretory Pathway

(all 15)

PubMed

31545789 Full text @ PLoS Genet.

Abstract

During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how BMP ligands are secreted from BMP-producing cells. In this work, we show the dominant role of Marcksb controlling the secretory process of Bmp2b via interaction with Hsp70 in vivo. We firstly carefully characterized the role of Marcksb in promoting BMP signaling during dorsoventral axis formation through knockdown approach. We then showed that Marcksb cell autonomously regulates the trafficking of Bmp2b from producing cell to the extracellular space and both the total and the extracellular Bmp2b was decreased in Marcksb-deficient embryos. However, neither the zygotic mutant of marcksb (Zmarcksb) nor the maternal zygotic mutant of marcksb (MZmarcksb) showed any defects of dorsalization. In contrast, the MZmarcksb embryos even showed increased BMP signaling activity as measured by expression of BMP targets, phosphorylated Smad1/5/9 levels and imaging of Bmp2b, suggesting that a phenomenon of "genetic over-compensation" arose. Finally, we revealed that the over-compensation effects of BMP signaling in MZmarcksb was achieved through a sequential up-regulation of MARCKS-family members Marcksa, Marcksl1a and Marcksl1b, and MARCKS-interacting protein Hsp70.3. We concluded that the Marcksb modulates BMP signaling through regulating the secretory pathway of Bmp2b.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
chrd	AB	standard conditions	Shield	shield	ISH	Fig 1
chrd	AB + MO1-marcksb	standard conditions	Shield	shield	ISH	Fig 1
eve1	AB	standard conditions	75%-epiboly	margin ventral region	ISH	Fig 1
eve1	AB + MO1-marcksb	standard conditions	75%-epiboly	margin ventral region	ISH	Fig 1
foxi1	AB	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 1
foxi1	AB	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 8
foxi1	AB + MO1-hsp70.3	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 8
foxi1	AB + MO1-hsp70.3 + MO1-marcksb	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 8
foxi1	AB + MO1-marcksb	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 8
foxi1	AB + MO1-marcksb	standard conditions	75%-epiboly	non neural ectoderm	ISH	Fig 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-chrd	standard conditions	Shield	whole organism ventral region szl expression increased distribution, abnormal	Fig 6
AB + MO1-chrd	standard conditions	Shield	whole organism ventral region ved expression increased distribution, abnormal	Fig 6
AB + MO1-chrd	standard conditions	Prim-5	whole organism ventralized, abnormal	Fig 6
AB + MO1-hsp70.3	standard conditions	Shield	whole organism ventral region szl expression decreased amount, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	Shield	whole organism ventral region szl expression decreased distribution, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	Shield	whole organism ventral region ved expression decreased amount, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	Shield	whole organism ventral region ved expression decreased distribution, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	75%-epiboly	neuroectoderm otx2b expression increased amount, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	75%-epiboly	neuroectoderm otx2b expression increased distribution, abnormal	Fig 8
AB + MO1-hsp70.3	standard conditions	75%-epiboly	non neural ectoderm foxi1 expression decreased amount, abnormal	Fig 8

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
ihb199	Small Deletion	marcksb
ihb200	Indel	marcksb
ta72a	Point Mutation	bmp2b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
chrd	MO1-chrd	MRPHLNO
hsp70.1	MO1-hsp70.3	MRPHLNO
hsp70.3	MO1-hsp70.3	MRPHLNO
hsp70l	CRISPR2-hsp70l	CRISPR
marcksa	CRISPR1-marcksa	CRISPR
marcksa	MO1-marcksa	MRPHLNO
marcksb	CRISPR1-marcksb	CRISPR
marcksb	MO1-marcksb	MRPHLNO
marcksl1a	CRISPR1-marcksl1a	CRISPR
marcksl1a	MO1-marcksl1a	MRPHLNO

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Fish

Fish
AB
AB + MO1-chrd
AB + MO1-hsp70.3
AB + MO1-hsp70.3 + MO1-marcksb
AB + MO1-marcksb
marcksb^{ihb199/ihb199}
marcksb^{ihb199/ihb199} + CRISPR1-marcksa + CRISPR1-marcksl1a + CRISPR1-marcksl1b
marcksb^{ihb199/ihb199} + CRISPR2-hsp70l
marcksb^{ihb199/ihb199} + MO1-chrd
marcksb^{ihb199/ihb199} + MO1-hsp70.3

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab13-smad	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Ye et al., 2019 ZDB-PUB-190924-12 PMID:31545789

Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b

Ye et al., 2019

ZDB-PUB-190924-12
PMID:31545789