PUBLICATION

Myogenin promotes myocyte fusion to balance fibre number and size

Authors

Ganassi, M., Badodi, S., Ortuste Quiroga, H.P., Zammit, P.S., Hinits, Y., Hughes, S.M.

ID

ZDB-PUB-181014-2

Date

2018

Source

Nature communications 9: 4232 (Journal)

Registered Authors

Hinits, Yaniv, Hughes, Simon M.

Keywords

none

MeSH Terms

Cells, Cultured
Muscle Cells/cytology
Muscle Cells/metabolism
Male
Myogenin/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Zebrafish/metabolism*
Animals
NADH Tetrazolium Reductase/metabolism
Female
RNA, Messenger/metabolism*
Chromatin Immunoprecipitation
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/metabolism

(all 14)

PubMed

30315160 Full text @ Nat. Commun.

Abstract

Each skeletal muscle acquires its unique size before birth, when terminally differentiating myocytes fuse to form a defined number of multinucleated myofibres. Although mice in which the transcription factor Myogenin is mutated lack most myogenesis and die perinatally, a specific cell biological role for Myogenin has remained elusive. Here we report that loss of function of zebrafish myog prevents formation of almost all multinucleated muscle fibres. A second, Myogenin-independent, fusion pathway in the deep myotome requires Hedgehog signalling. Lack of Myogenin does not prevent terminal differentiation; the smaller myotome has a normal number of myocytes forming more mononuclear, thin, albeit functional, fast muscle fibres. Mechanistically, Myogenin binds to the myomaker promoter and is required for expression of myomaker and other genes essential for myocyte fusion. Adult myog mutants display reduced muscle mass, decreased fibre size and nucleation. Adult-derived myog mutant myocytes show persistent defective fusion ex vivo. Myogenin is therefore essential for muscle homeostasis, regulating myocyte fusion to determine both muscle fibre number and size.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
myog^fh265/fh265 (AB)	standard conditions	Adult	whole organism weight, normal	Fig. 7
myog^kg125/kg125 (TL)	control	20-25 somites	myotome skeletal muscle tissue development decreased process quality, abnormal	Fig. 6
myog^kg125/kg125 (TL)	control	20-25 somites	somite skeletal muscle cell mymk expression decreased amount, abnormal	Fig. 6
myog^kg125/kg125 (TL)	control	20-25 somites	whole organism mymk expression decreased amount, abnormal	Fig. 6
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	myotome skeletal muscle cell myog expression absent, abnormal	Fig. 1
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	myotome skeletal muscle cell myog expression decreased amount, abnormal	Fig. 1
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	myotome skeletal muscle tissue development decreased process quality, abnormal	Fig. 6
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	skeletal muscle cell nucleus myog expression absent, abnormal	Fig. 1
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	somite skeletal muscle cell mymk expression decreased amount, abnormal	Fig. 6
myog^kg125/kg125 (TL)	standard conditions	20-25 somites	whole organism jam3b expression decreased amount, abnormal	Fig. 5

1 - 10 of 52

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fh261		Point Mutation	myod1
fh265		Point Mutation	myog
kg125		Small Deletion	myog
kg128		Insertion	myog
vu119Tg	Tg(Ola.Actb:Hsa.HRAS-EGFP)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
myog	CRISPR1-myog	CRISPR
myog	MO1-myog	MRPHLNO

Fish

Fish
myod1^fh261/fh261 (AB)
myog^fh265/fh265 (AB)
myog^kg125/kg125 (TL)
myog^kg125/kg125; vu119Tg
myog^kg128/kg128 (TL)
myog^kg128/kg128; vu119Tg
vu119Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Ganassi et al., 2018 ZDB-PUB-181014-2 PMID:30315160

Myogenin promotes myocyte fusion to balance fibre number and size

Ganassi et al., 2018

ZDB-PUB-181014-2
PMID:30315160