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The role of Maged1 in skeletal muscle myogenesis

Danielle Fowler

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Abstract

regulation of skeletal muscle growth may play an important role in the development of future treatments for patients suffering from muscle loss due to aging, disease or injury. Knowledge concerning which factors can activate skeletal myogenesis will facilitate the advancement of stem cell therapies to replace damaged tissue. Melanoma antigen gene-D1 (Maged1) is a member of the MAGE family of proteins that has recently been shown to be important in terminal skeletal myogenesis. It is known to alleviate Msxdependent repression of myogenic genes during terminal myoblast differentiation (1). Our lab has linked Maged1 to an important early developmental transcription factor Pax3 through CoImmunoprecipitation (CoIP) and mass spectrometry experiments. Pax3 is expressed in myogenic progenitors and plays a role in the activation of myogenic regulatory factors. To further study the role of Maged1 in skeletal myogenesis, we examined the differentiation of shMaged1 mouse embryonic stem cells (mESc). Quantitative polymerase chain reaction (qPCR) was used to investigate the impact of the knockdown on important myogenic genes. The knockdown resulted in a significant decrease in the expression of myogenic regulatory factors, Myogenin, MyoD and myogenic progenitor marker Pax3. Trends towards reduced expression of mesodermal marker Brachyury T and myogenic regulatory factor Myf5 were also observed. These results show that Maged1 is important for the expression of important myogenic genes required for embryonic skeletal myogenesis.

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What this paper is about

regulation of skeletal muscle growth may play an important role in the development of future treatments for patients suffering from muscle loss due to aging, disease or injury. Knowledge concerning which factors can activate skeletal myogenesis will facilitate the advancement of stem cell therapies to replace damaged tissue. Melanoma antigen gene-D1 (Maged1) is a member of the MAGE family of proteins that has recently been shown to be important in terminal skeletal myogenesis. It is known to alleviate Msxdependent repression of myogenic genes during terminal myoblast differentiation (1). Our lab has linked Maged1 to an important early developmental transcription factor Pax3 through CoImmunoprecipitation (CoIP) and mass spectrometry experiments. Pax3 is expressed in myogenic progenitors and plays a role in the activation of myogenic regulatory factors. To further study the role of Maged1 in skeletal myogenesis, we examined the differentiation of shMaged1 mouse embryonic stem cells (mESc). Quantitative polymerase chain reaction (qPCR) was used to investigate the impact of the knockdown on important myogenic genes. The knockdown resulted in a significant decrease in the expression of myogenic regulatory factors, Myogenin, MyoD and myogenic progenitor marker Pax3. Trends towards reduced expression of mesodermal marker Brachyury T and myogenic regulatory factor Myf5 were also observed. These results show that Maged1 is important for the expression of important myogenic genes required for embryonic skeletal myogenesis.

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Available abstract

regulation of skeletal muscle growth may play an important role in the development of future treatments for patients suffering from muscle loss due to aging, disease or injury. Knowledge concerning which factors can activate skeletal myogenesis will facilitate the advancement of stem cell therapies to replace damaged tissue. Melanoma antigen gene-D1 (Maged1) is a member of the MAGE family of proteins that has recently been shown to be important in terminal skeletal myogenesis. It is known to alleviate Msxdependent repression of myogenic genes during terminal myoblast differentiation (1). Our lab has linked Maged1 to an important early developmental transcription factor Pax3 through CoImmunoprecipitation (CoIP) and mass spectrometry experiments. Pax3 is expressed in myogenic progenitors and plays a role in the activation of myogenic regulatory factors. To further study the role of Maged1 in skeletal myogenesis, we examined the differentiation of shMaged1 mouse embryonic stem cells (mESc). Quantitative polymerase chain reaction (qPCR) was used to investigate the impact of the knockdown on important myogenic genes. The knockdown resulted in a significant decrease in the expression of myogenic regulatory factors, Myogenin, MyoD and myogenic progenitor marker Pax3. Trends towards reduced expression of mesodermal marker Brachyury T and myogenic regulatory factor Myf5 were also observed. These results show that Maged1 is important for the expression of important myogenic genes required for embryonic skeletal myogenesis.

Key concepts: Myogenesis, MYF5, Myogenin, MyoD, Myogenic regulatory factors, PAX3, Skeletal muscle, Biology

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