Abstract
BackgroundCell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood.MethodsTo gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair.ResultsHigh levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro.ConclusionsOur results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function.
Highlights
Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis
Our results showed that muscle-specific expression of a dominant negative Ste20-like kinase (SLK) reduces overall kinase activity in muscle tissue, and affects muscle development and litter size
Generation of SLK transgenic mice We have previously shown that SLK is highly expressed in both the neuronal and myogenic compartment in the developing embryo [31]
Summary
Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. Growth and differentiation of muscle cells are regulated by complex processes involving a large number of signaling systems. Several members of the Ste family of kinases have been identified in mammals [8], and have been shown to play a role in various biological processes such as stress, cell death, cytoskeletal reorganization, growth, and differentiation [9,10,11,12,13,14,15]. A role for SLK in cell migration and cell-cycle progression has been shown [23,24,25,26,27,28,29,30]
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