The zebrafish slow-muscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2189-2199 ◽  
Author(s):  
M.J. Barresi ◽  
H.L. Stickney ◽  
S.H. Devoto

Hedgehog proteins mediate many of the inductive interactions that determine cell fate during embryonic development. Hedgehog signaling has been shown to regulate slow muscle fiber type development. We report here that mutations in the zebrafish slow-muscle-omitted (smu) gene disrupt many developmental processes involving Hedgehog signaling. smu(−/−) embryos have a 99% reduction in the number of slow muscle fibers and a complete loss of Engrailed-expressing muscle pioneers. In addition, mutant embryos have partial cyclopia, and defects in jaw cartilage, circulation and fin growth. The smu(−/−) phenotype is phenocopied by treatment of wild-type embryos with forskolin, which inhibits the response of cells to Hedgehog signaling by indirect activation of cAMP-dependent protein kinase (PKA). Overexpression of Sonic hedgehog (Shh) or dominant negative PKA (dnPKA) in wild-type embryos causes all somitic cells to develop into slow muscle fibers. Overexpression of Shh does not rescue slow muscle fiber development in smu(−/−) embryos, whereas overexpression of dnPKA does. Cell transplantation experiments confirm that smu function is required cell-autonomously within the muscle precursors: wild-type muscle cells rescue slow muscle fiber development in smu(−/−) embryos, whereas mutant muscle cells cannot develop into slow muscle fibers in wild-type embryos. Slow muscle fiber development in smu mutant embryos is also rescued by expression of rat Smoothened. Therefore, Hedgehog signaling through Slow-muscle-omitted is necessary for slow muscle fiber type development. We propose that smu encodes a vital component in the Hedgehog response pathway.

2019 ◽  
Vol 10 (6) ◽  
pp. 3334-3343 ◽  
Author(s):  
Qinyang Jiang ◽  
Xiaofang Cheng ◽  
Yueyue Cui ◽  
Qin Xia ◽  
Xueyu Yan ◽  
...  

This study was conducted to investigate the effect and underlying mechanism of Resveratrol (RES) in regulating skeletal muscle fiber-type switching.


2013 ◽  
Vol 115 (5) ◽  
pp. 723-729 ◽  
Author(s):  
James G. Hopker ◽  
Damian A. Coleman ◽  
Hannah C. Gregson ◽  
Simon A. Jobson ◽  
Tobias Von der Haar ◽  
...  

The purpose of this study was to assess the influence of age, training status, and muscle fiber-type distribution on cycling efficiency. Forty men were recruited into one of four groups: young and old trained cyclists, and young and old untrained individuals. All participants completed an incremental ramp test to measure their peak O2 uptake, maximal heart rate, and maximal minute power output; a submaximal test of cycling gross efficiency (GE) at a series of absolute and relative work rates; and, in trained participants only, a 1-h cycling time trial. Finally, all participants underwent a muscle biopsy of their right vastus lateralis muscle. At relative work rates, a general linear model found significant main effects of age and training status on GE ( P < 0.01). The percentage of type I muscle fibers was higher in the trained groups ( P < 0.01), with no difference between age groups. There was no relationship between fiber type and cycling efficiency at any work rate or cadence combination. Stepwise multiple regression indicated that muscle fiber type did not influence cycling performance ( P > 0.05). Power output in the 1-h performance trial was predicted by average O2 uptake and GE, with standardized β-coefficients of 0.94 and 0.34, respectively, although some mathematical coupling is evident. These data demonstrate that muscle fiber type does not affect cycling efficiency and was not influenced by the aging process. Cycling efficiency and the percentage of type I muscle fibers were influenced by training status, but only GE at 120 revolutions/min was seen to predict cycling performance.


1983 ◽  
Vol 55 (5) ◽  
pp. 1386-1392 ◽  
Author(s):  
G. C. Sieck ◽  
R. R. Roy ◽  
P. Powell ◽  
C. Blanco ◽  
V. R. Edgerton ◽  
...  

Three types of diaphragmatic muscle fibers were identified histochemically in the sternal, costal, and crural regions of the cat diaphragm. Differences in the proportion of each muscle fiber type were observed between the abdominal and thoracic surfaces of the diaphragm but not among the different regions. A higher percentage of slow-twitch oxidative fibers was noted on the abdominal surface, whereas more fast-twitch fibers (fast-twitch oxidative-glycolytic and fast-twitch glycolytic) were found on the thoracic surface. Differences in muscle architecture were observed between diaphragmatic regions, but not between abdominal and thoracic sides. Overall, muscle fibers were longer in the crural regions, with the longest fibers being found in the crossing-band area of the crura. In the costal regions, fibers were longest in the center and became shorter toward the ventral and dorsal extent of these regions. Fiber lengths were similar throughout the sternal region. In each diaphragmatic region, the length of fibers extended from the origin of the muscle to its insertion. We conclude that functional differences between diaphragmatic regions could be attributed to fiber length and/or orientation, but not to differences in fiber-type composition.


2014 ◽  
Vol 207 (6) ◽  
pp. 753-766 ◽  
Author(s):  
Duo Zhang ◽  
Xiaoyun Wang ◽  
Yuying Li ◽  
Lei Zhao ◽  
Minghua Lu ◽  
...  

It is known that thyroid hormone (TH) is a major determinant of muscle fiber composition, but the molecular mechanism by which it does so remains unclear. Here, we demonstrated that miR-133a1 is a direct target gene of TH in muscle. Intriguingly, miR-133a, which is enriched in fast-twitch muscle, regulates slow-to-fast muscle fiber type conversion by targeting TEA domain family member 1 (TEAD1), a key regulator of slow muscle gene expression. Inhibition of miR-133a in vivo abrogated TH action on muscle fiber type conversion. Moreover, TEAD1 overexpression antagonized the effect of miR-133a as well as TH on muscle fiber type switch. Additionally, we demonstrate that TH negatively regulates the transcription of myosin heavy chain I indirectly via miR-133a/TEAD1. Collectively, we propose that TH inhibits the slow muscle phenotype through a novel epigenetic mechanism involving repression of TEAD1 expression via targeting by miR-133a1. This identification of a TH-regulated microRNA therefore sheds new light on how TH achieves its diverse biological activities.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009488
Author(s):  
Liwei Xiao ◽  
Jing Liu ◽  
Zongchao Sun ◽  
Yujing Yin ◽  
Yan Mao ◽  
...  

Mitochondria are essential for maintaining skeletal muscle metabolic homeostasis during adaptive response to a myriad of physiologic or pathophysiological stresses. The mechanisms by which mitochondrial function and contractile fiber type are concordantly regulated to ensure muscle function remain poorly understood. Evidence is emerging that the Folliculin interacting protein 1 (Fnip1) is involved in skeletal muscle fiber type specification, function, and disease. In this study, Fnip1 was specifically expressed in skeletal muscle in Fnip1-transgenic (Fnip1Tg) mice. Fnip1Tg mice were crossed with Fnip1-knockout (Fnip1KO) mice to generate Fnip1TgKO mice expressing Fnip1 only in skeletal muscle but not in other tissues. Our results indicate that, in addition to the known role in type I fiber program, FNIP1 exerts control upon muscle mitochondrial oxidative program through AMPK signaling. Indeed, basal levels of FNIP1 are sufficient to inhibit AMPK but not mTORC1 activity in skeletal muscle cells. Gain-of-function and loss-of-function strategies in mice, together with assessment of primary muscle cells, demonstrated that skeletal muscle mitochondrial program is suppressed via the inhibitory actions of FNIP1 on AMPK. Surprisingly, the FNIP1 actions on type I fiber program is independent of AMPK and its downstream PGC-1α. These studies provide a vital framework for understanding the intrinsic role of FNIP1 as a crucial factor in the concerted regulation of mitochondrial function and muscle fiber type that determine muscle fitness.


1971 ◽  
Vol 32 (1) ◽  
pp. 57-61 ◽  
Author(s):  
H. B. Hendricks ◽  
D. T. Lafferty ◽  
E. D. Aberle ◽  
M. D. Judge ◽  
J. C. Forrest

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