PUBLICATION

Cdkn1c drives muscle differentiation through a positive feedback loop with Myod

Authors

Osborn, D.P., Li, K., Hinits, Y., and Hughes, S.M.

ID

ZDB-PUB-101222-7

Date

2011

Source

Developmental Biology 350(2): 464-475 (Journal)

Registered Authors

Hinits, Yaniv, Hughes, Simon M., Li, Kuoyu, Osborn, Dan

Keywords

Muscle, Cdkn1c, Zebrafish, Hedgehog, Myod, Myog, p57kip2

MeSH Terms

Animals
Hedgehog Proteins/physiology
Zebrafish
Feedback, Physiological
Cyclin-Dependent Kinase Inhibitor p57/physiology*
Cell Differentiation
MyoD Protein/physiology*
Myogenin/genetics
Myogenic Regulatory Factor 5/physiology
Signal Transduction
Muscle Development*

(all 11)

PubMed

21147088 Full text @ Dev. Biol.

Abstract

Differentiation often requires conversion of analogue signals to a stable binary output through positive feedback. Hedgehog (Hh) signalling promotes myogenesis in the vertebrate somite, in part by raising the activity of muscle regulatory factors (MRFs) of the Myod family above a threshold. Hh is known to enhance MRF expression. Here we show that Hh is also essential at a second step that increases Myod protein activity, permitting it to promote Myogenin expression. Hh acts by inducing expression of cdkn1c (p57(Kip2)) in slow muscle precursor cells, but neither Hh nor Cdkn1c is required for their cell cycle exit. Cdkn1c co-operates with Myod to drive differentiation of several early zebrafish muscle fibre types. Myod in turn up-regulates cdkn1c, thereby providing a positive feedback loop that switches myogenic cells to terminal differentiation.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
cdkn1a	WT	standard conditions	14-19 somites	Not Detected	adaxial cell	ISH	Fig. S4
cdkn1ba	WT	standard conditions	14-19 somites	Not Detected	adaxial cell	ISH	Fig. S4
cdkn1bb	WT	standard conditions	14-19 somites	Not Detected	adaxial cell	ISH	Fig. S4
cdkn1bb	WT	standard conditions	14-19 somites		somite lateral region	ISH	Fig. S4
cdkn1ca	myf5^{hu2022/hu2022}	control	10-13 somites to 14-19 somites		adaxial cell	ISH	Fig. 4
cdkn1ca	myf5^{hu2022/hu2022}	control	10-13 somites to 14-19 somites		somite	ISH	Fig. 4
cdkn1ca	myf5^{hu2022/hu2022}	control	10-13 somites to 14-19 somites		tail bud	ISH	Fig. 4
cdkn1ca	myf5^{hu2022/hu2022} + MO1-myod1	standard conditions	10-13 somites to 14-19 somites	Not Detected	adaxial cell	ISH	Fig. 4
cdkn1ca	myf5^{hu2022/hu2022} + MO1-myod1	standard conditions	10-13 somites to 14-19 somites		tail bud	ISH	Fig. 4
cdkn1ca	shha^{tbx392/tbx392}	standard conditions	5-9 somites		adaxial cell	ISH	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-myod1	standard conditions	5-9 somites	skeletal muscle tissue development delayed, abnormal	Fig. 2
WT + MO1-myod1	standard conditions	Prim-5	fast muscle cell decreased amount, abnormal	Fig. 6
WT + MO1-myod1	standard conditions	Protruding-mouth	head muscle hypoplastic, abnormal	Fig. 6
WT + MO1-myod1 + MO3-cdkn1ca	standard conditions	Prim-5	fast muscle cell decreased amount, abnormal	Fig. 6
WT + MO1-myod1 + MO3-cdkn1ca	standard conditions	Protruding-mouth	head muscle hypoplastic, abnormal	Fig. 6
WT + MO1-myog	standard conditions	5-9 somites	skeletal muscle tissue development delayed, abnormal	Fig. 2
WT + MO2-cdkn1ca	standard conditions	Bud	adaxial cell decreased amount, abnormal	Fig. 3
WT + MO3-cdkn1ca	standard conditions	5-9 somites	adaxial cell decreased amount, abnormal	Fig. 3
WT + MO3-cdkn1ca	standard conditions	Prim-5	fast muscle cell decreased amount, abnormal	Fig. 6
WT + MO3-cdkn1ca	standard conditions	Prim-5	slow muscle cell normal amount, normal	Fig. 6

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
b641	Point Mutation	smo
hu2022	Point Mutation	myf5
tbx392	Point Mutation	shha

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdkn1ca	MO1-cdkn1ca	MRPHLNO
cdkn1ca	MO2-cdkn1ca	MRPHLNO
cdkn1ca	MO3-cdkn1ca	MRPHLNO
myf5	MO3-myf5	MRPHLNO
myod1	MO1-myod1	MRPHLNO
myog	MO1-myog	MRPHLNO

Fish

Fish
myf5^{hu2022/hu2022}
myf5^{hu2022/hu2022} + MO1-myod1
myf5^{hu2022/hu2022} + MO1-myod1 + MO3-cdkn1ca
shha^{tbx392/tbx392}
shha^{tbx392/tbx392} + MO1-myod1
shha^{tbx392/tbx392} + MO1-myog
shha^{tbx392/tbx392} + MO3-cdkn1ca
shha^{tbx392/tbx392} + MO3-myf5
smo^b641/b641
WT

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Antibodies

Orthology

Engineered Foreign Genes

Mapping

Osborn et al., 2011 ZDB-PUB-101222-7 PMID:21147088

Cdkn1c drives muscle differentiation through a positive feedback loop with Myod

Osborn et al., 2011

ZDB-PUB-101222-7
PMID:21147088