scholarly journals Transcriptional regulation of myotube fate specification and intrafusal muscle fiber morphogenesis

2005 ◽  
Vol 169 (2) ◽  
pp. 257-268 ◽  
Author(s):  
Y'vonne Albert ◽  
Jennifer Whitehead ◽  
Laurie Eldredge ◽  
John Carter ◽  
Xiaoguang Gao ◽  
...  

Vertebrate muscle spindle stretch receptors are important for limb position sensation (proprioception) and stretch reflexes. The structurally complex stretch receptor arises from a single myotube, which is transformed into multiple intrafusal muscle fibers by sensory axon–dependent signal transduction that alters gene expression in the contacted myotubes. The sensory-derived signal transduction pathways that specify the fate of myotubes are very poorly understood. The zinc finger transcription factor, early growth response gene 3 (Egr3), is selectively expressed in sensory axon–contacted myotubes, and it is required for normal intrafusal muscle fiber differentiation and spindle development. Here, we show that overexpression of Egr3 in primary myotubes in vitro leads to the expression of a particular repertoire of genes, some of which we demonstrate are also regulated by Egr3 in developing intrafusal muscle fibers within spindles. Thus, our results identify a network of genes that are regulated by Egr3 and are involved in intrafusal muscle fiber differentiation. Moreover, we show that Egr3 mediates myotube fate specification that is induced by sensory innervation because skeletal myotubes that express Egr3 independent of other sensory axon regulation are transformed into muscle fibers with structural and molecular similarities to intrafusal muscle fibers. Hence, Egr3 is a target gene that is regulated by sensory innervation and that mediates gene expression involved in myotube fate specification and intrafusal muscle fiber morphogenesis.

1999 ◽  
Vol 81 (6) ◽  
pp. 2823-2832 ◽  
Author(s):  
Julien Petit ◽  
Robert W. Banks ◽  
Yves Laporte

Testing the classification of static γ axons using different patterns of random stimulation. The possibility of using randomly generated stimulus intervals (with a Poisson distribution) to identify the type(s) of intrafusal fiber activated by the stimulation of single static γ axons was tested in Peroneus tertius muscle spindles of anesthetized cats. Three patterns of random stimulation with different values of mean intervals [20 ± 4.47, 30 ± 8.94, and 40 ± 8.94 (SD) ms] were used. Single static γ axons activating, in single spindles, either the bag2 fiber alone or the chain fibers alone or both types of intrafusal fiber were prepared. Responses of spindle primary endings elicited by the stimulation of γ axons were recorded from Ia fibers in cut dorsal root filaments. Cross-correlograms between stimuli and spikes of the primary ending responses, autocorrelograms, interval histograms of responses, and stimulations were built. The characteristics of cross-correlograms were found to be related not only to the type of intrafusal muscle fibers activated but also to the parameters of the stimulation. Moreover some cross-correlograms with similar characteristics were produced by the activation of different intrafusal muscle fibers. It also was observed that, whatever the type of intrafusal muscle fiber activated, cross-correlograms could exhibit oscillations after an initial peak, provided the extent in frequency of the primary ending response was small; these oscillations arise in part from the autocorrelation of the primary ending responses. Therefore, cross-correlograms obtained during random stimulation of static γ axons cannot be used for unequivocally identifying the type(s) of intrafusal muscle fiber these axons supply.


1971 ◽  
Vol 51 (1) ◽  
pp. 83-103 ◽  
Author(s):  
William K. Ovalle

An ultrastructural comparison of the two types of intrafusal muscle fibers in muscle spindles of the rat was undertaken. Discrete myofibrils with abundant interfibrillar sarcoplasm and organelles characterize the nuclear chain muscle fiber, while a continuous myofibril-like bundle with sparse interfibrillar sarcoplasm distinguishes the nuclear bag muscle fiber. Nuclear chain fibers possess well-defined and typical M bands in the center of each sarcomere, while nuclear bag fibers contain ill-defined M bands composed of two parallel thin densities in the center of the pseudo-H zone of each sarcomere. Mitochondria of nuclear chain fibers are larger and more numerous than they are in nuclear bag fibers. Mitochondria of chain fibers, in addition, often contain conspicuous dense granules, and they are frequently intimately related to elements of the sarcoplasmic reticulum (SR). Striking differences are noted in the organization and degree of development of the sarcotubular system. Nuclear bag fibers contain a poorly developed SR and T system with only occasional junctional couplings (dyads and triads). Nuclear chain fibers, in contrast, possess an unusually well-developed SR and T system and a variety of multiple junctional couplings (dyads, triads, quatrads, pentads, septads). Greatly dilated SR cisternae are common features of nuclear chain fibers, often forming intimate associations with T tubules, mitochondria, and the sarcolemma. Such dilatations of the SR were not encountered in nuclear bag fibers. The functional significance of these structural findings is discussed.


1978 ◽  
Vol 26 (11) ◽  
pp. 973-988 ◽  
Author(s):  
J Kucera ◽  
K Dorovini-Zis ◽  
W K Engel

Muscle spindles were followed in serial transverse sections of freshly frozen rat soleus muscles. Adenosine triphosphatase (ATPase) histochemical staining reaction was used to identify nuclear bag1, nuclear bag2 and nuclear chain intrafusal muscle fibers. Regional differences in ATPase staining occurred along bag1 and bag2 fibers but not along chain fibers. Bag1 fibers displayed ultrastructural heterogenity when their intra- and extracapsular regions were compared. Simple "diffuse" and more elaborate "plate" motor nerve terminals were demonstrated histochemically along the poles of bag1 and bag2 fibers by staining for cholinesterase. One motor terminal of the "plate" appearance was present on a chain fiber pole. There was no consistent spatial correlation between the intensity of regional ATPase staining along the nuclear bag fibers and the location, number and type of motor endings. Other factors, such as intrafusal fiber sensory innervation and regional differences in active and passive functional recruitment of nuclear bag fibers during muscle activity, may contribute to the ATPase staining variability along the intrafusal fibers.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Aynur Kaya-Çopur ◽  
Fabio Marchiano ◽  
Marco Y Hein ◽  
Daniel Alpern ◽  
Julie Russeil ◽  
...  

Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the large Drosophila flight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.


1972 ◽  
Vol 50 (3) ◽  
pp. 195-202 ◽  
Author(s):  
W. K. Ovalle ◽  
R. S. Smith

Serial frozen section of muscle spindles in the lumbrical muscles of the cat and the monkey were tested with a recently described modification of the myosin ATPase reaction (Guth and Samaha 1970. Exp. Neurol 28, 365). This reaction is able to detect acid-stable, alkaline-labile myosin ATPase and acid-labile, alkaline-stable myosin ATPase. The reactions were carried out by preincubation of the sections at pH 10.4 or 4.35 with incubation in a substrate at pH 9.4. In both the cat and the monkey three types of intrafusal muscle fibers could be detected on the basis of their reaction for myosin ATPase. Nuclear bag fibers could be divided into two types: those containing the acid-stable form of myosin ATPase only, and those containing ATPase detectable under both acid and alkaline conditions. Nuclear chain fibers contained the alkaline-stable form of ATPase only.


1990 ◽  
Vol 93 (6) ◽  
pp. 567-580 ◽  
Author(s):  
J. Kucera ◽  
J. M. Walro

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