PUBLICATION

Myoneurin regulates BMP signaling by competing with Ppm1a for Smad binding

Authors: Yang, S., Ning, G., Hou, Y., Cao, Y., Xu, J., Wu, J., Zhang, T., Wang, Q.
ID: ZDB-PUB-220622-19
Date: 2022
Source: iScience 25: 104495 (Journal)
Registered Authors: Wang, Qiang
Keywords: Cell biology, Developmental biology, Functional aspects of cell biology
MeSH Terms: none
PubMed: 35712083 Full text @ iScience

Abstract

A delicate balance of BMP activity is critical for tissue formation and organogenesis. However, the mechanical molecular details in ensuring the proper duration and intensity of BMP signaling have yet to be fully elucidated. Here, we identified a zebrafish mutant with a disrupted gene encoding for the BTB/POZ and zinc finger protein myoneurin (Mynn). mynn^-/- mutants exhibited severe loss of pharyngeal cartilage elements, owing to poor proliferation, blocked differentiation, and low viability of cranial neural crest cells. Depletion of mynn in both zebrafish embryos and mammalian cells led to a reduction of the BMP signal activity. Mechanistically, Mynn interacts with Smad proteins in the nucleus, thereby disrupting the association between Smad protein and the phosphatase Ppm1a. Ultimately, this interaction prevents Smad dephosphorylation. More broadly, our findings may provide a new strategy to balance BMP signal activity via competitive binding of Mynn and Ppm1a to Smad proteins during pharyngeal cartilage formation.

Genes / Markers

Marker	Marker Type	Name
col2a1a	GENE	collagen, type II, alpha 1a
dlx2a	GENE	distal-less homeobox 2a
gadd45aa	GENE	growth arrest and DNA-damage-inducible, alpha, a
hand2	GENE	heart and neural crest derivatives expressed 2
id1	GENE	inhibitor of DNA binding 1, HLH protein
mynn	GENE	myoneurin
ppm1aa	GENE	protein phosphatase, Mg2+/Mn2+ dependent, 1Aa
sox9a	GENE	SRY-box transcription factor 9a
tp53	GENE	tumor protein p53

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Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Prim-5	central nervous system mynn expression decreased amount, abnormal	Fig. 2
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Prim-5	central nervous system mynn expression decreased distribution, abnormal	Fig. 2
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	brain gadd45aa expression increased distribution, abnormal	Fig. 4
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	brain tp53 expression increased distribution, abnormal	Fig. 4
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	eye gadd45aa expression increased distribution, abnormal	Fig. 4
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	eye tp53 expression increased distribution, abnormal	Fig. 4
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	eye decreased size, abnormal	Fig. 1
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	head decreased size, abnormal	Fig. 1
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	integument rough, abnormal	Fig. 1
mynn^{ioz054Gt/ioz054Gt}	standard conditions	Long-pec	pharyngeal arch 1 apoptotic process increased process quality, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ioz054Gt	Gt(T2EGE)	Transgenic Insertion	mynn
pt509Tg	Tg1(BMPRE:EGFP)	Transgenic Insertion
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion
zdf1		Point Mutation	tp53

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
mynn	MO1-mynn	MRPHLNO
ppm1aa	MO1-ppm1aa	MRPHLNO

Fish

Fish
mynn^{ioz054Gt/ioz054Gt}
mynn^{ioz054Gt/ioz054Gt}; pt509Tg
mynn^{ioz054Gt/ioz054Gt}; y1Tg
mynn^{ioz054Gt/ioz054Gt}; y1Tg + MO1-ppm1aa
mynn^ioz054Gt/+
pt509Tg
tp53^zdf1/zdf1; mynn^{ioz054Gt/ioz054Gt}
WT
y1Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Yang et al., 2022 ZDB-PUB-220622-19 PMID:35712083

Myoneurin regulates BMP signaling by competing with Ppm1a for Smad binding

Yang et al., 2022

ZDB-PUB-220622-19
PMID:35712083