How Do We Build a Muscle? Let Me Count the Genes...

Disciplines

Cell and Developmental Biology | Genetics and Genomics

Abstract (300 words maximum)

Akirin is a nuclear cofactor involved in the gene regulation of embryonic heart patterning in Drosophila melanogaster. During development, Akirin facilitates gene expression by integrating Twist transcription factor activity with chromatin remodeling machinery to facilitate the proper level of Twist-regulated gene expression. Our data indicates that Akirin regulates cardiac and skeletal muscle patterning through interactions with both SWI/SNF-class and NuRD/CHD4- class chromatin remodeling complexes. Excitingly, this mechanism appears to be conserved from insects to mammals and other metazoans. We are employing a combination of forward genetic screens paired with live imaging analysis of cardiac function to uncover novel genetic loci that may work with Akirin during skeletal and cardiac patterning. To date, we have uncovered several loci that appear to fit these criteria. Our current work centers on two of these candidate loci, hyd and Ppn, both of which appear to interact with akirin during these developmental events. The identification of these novel Akirin interactors will yield new insights into the mechanisms by which cofactors such as Akirin are critical for developmental processes.

Academic department under which the project should be listed

CSM - Molecular and Cellular Biology

Primary Investigator (PI) Name

Scott Nowak

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How Do We Build a Muscle? Let Me Count the Genes...

Akirin is a nuclear cofactor involved in the gene regulation of embryonic heart patterning in Drosophila melanogaster. During development, Akirin facilitates gene expression by integrating Twist transcription factor activity with chromatin remodeling machinery to facilitate the proper level of Twist-regulated gene expression. Our data indicates that Akirin regulates cardiac and skeletal muscle patterning through interactions with both SWI/SNF-class and NuRD/CHD4- class chromatin remodeling complexes. Excitingly, this mechanism appears to be conserved from insects to mammals and other metazoans. We are employing a combination of forward genetic screens paired with live imaging analysis of cardiac function to uncover novel genetic loci that may work with Akirin during skeletal and cardiac patterning. To date, we have uncovered several loci that appear to fit these criteria. Our current work centers on two of these candidate loci, hyd and Ppn, both of which appear to interact with akirin during these developmental events. The identification of these novel Akirin interactors will yield new insights into the mechanisms by which cofactors such as Akirin are critical for developmental processes.