TY - JOUR

T1 - Six1 homeoprotein drives myofiber type IIA specialization in soleus muscle

AU - Sakakibara, Iori

AU - Wurmser, Maud

AU - Dos Santos, Matthieu

AU - Santolini, Marc

AU - Ducommun, Serge

AU - Davaze, Romain

AU - Guernec, Anthony

AU - Sakamoto, Kei

AU - Maire, Pascal

PY - 2016/9/5

Y1 - 2016/9/5

N2 - Background: Adult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription factors regulating muscle cell fate through activation of myogenic regulatory factors and driving fast-type gene expression during embryogenesis. Results: We show here that Six1 protein accumulates more robustly in the nuclei of adult fast-type muscles than in adult slow-type muscles, this specific enrichment takes place during perinatal growth. Deletion of Six1 in soleus impaired fast-type myofiber specialization during perinatal development, resulting in a slow phenotype and a complete lack of Myosin heavy chain 2A (MyHCIIA) expression. Global transcriptomic analysis of wild-type and Six1 mutant myofibers identified the gene networks controlled by Six1 in adult soleus muscle. This analysis showed that Six1 is required for the expression of numerous genes encoding fast-type sarcomeric proteins, glycolytic enzymes and controlling intracellular calcium homeostasis. Parvalbumin, a key player of calcium buffering, in particular, is a direct target of Six1 in the adult myofiber. Conclusions: This analysis revealed that Six1 controls distinct aspects of adult muscle physiology in vivo, and acts as a main determinant of fast-fiber type acquisition and maintenance.

AB - Background: Adult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription factors regulating muscle cell fate through activation of myogenic regulatory factors and driving fast-type gene expression during embryogenesis. Results: We show here that Six1 protein accumulates more robustly in the nuclei of adult fast-type muscles than in adult slow-type muscles, this specific enrichment takes place during perinatal growth. Deletion of Six1 in soleus impaired fast-type myofiber specialization during perinatal development, resulting in a slow phenotype and a complete lack of Myosin heavy chain 2A (MyHCIIA) expression. Global transcriptomic analysis of wild-type and Six1 mutant myofibers identified the gene networks controlled by Six1 in adult soleus muscle. This analysis showed that Six1 is required for the expression of numerous genes encoding fast-type sarcomeric proteins, glycolytic enzymes and controlling intracellular calcium homeostasis. Parvalbumin, a key player of calcium buffering, in particular, is a direct target of Six1 in the adult myofiber. Conclusions: This analysis revealed that Six1 controls distinct aspects of adult muscle physiology in vivo, and acts as a main determinant of fast-fiber type acquisition and maintenance.

KW - Myosin heavy chain

KW - Pvalb

KW - Six1

KW - Skeletal muscle

KW - Slow and fast myofibers

KW - Soleus

UR - http://www.scopus.com/inward/record.url?scp=84984945154&partnerID=8YFLogxK

U2 - 10.1186/s13395-016-0102-x

DO - 10.1186/s13395-016-0102-x

M3 - Journal article

C2 - 27597886

AN - SCOPUS:84984945154

VL - 6

JO - Skeletal Muscle

JF - Skeletal Muscle

SN - 2044-5040

IS - 1

M1 - 30

ER -