Developmental biologist Mary Baylies studies the mechanisms that form and maintain muscle both during normal development and in disease.
Skeletal muscles come in a variety of shapes and sizes, each tuned to a particular function — from the muscles that allow a person to run to those that focus the eye. Individual muscles also have different susceptibilities to diseases like muscular dystrophy, muscle myopathies, and rhabdomyosarcoma.
Therapies that repair muscle wasting due to aging or disease require the ability to generate specific muscle types of a particular size and shape. Therefore, identifying the mechanisms of how muscles differentiate, as well as how they grow and respond to disease, is critical. My lab focuses on the following questions:
To assay muscle function, we use a larval crawling assay shown in this video clip. Larva on the right is a control and moves effortlessly towards an attractive odor. Larva on left has mispositioned nuclei in muscle. This larva cannot move efficiently.
Our primary model system is the Drosophila musculature, in which we employ genetics, molecular and cell biological approaches, bioinformatics, in vivo time-lapse imaging, and biochemistry to identify and characterize genes required for muscle formation, use, and maintenance. (See Figures 1, 2) We also use mammalian muscle models to confirm and extend the paradigms that we develop in Drosophila.
Currently, we study two significant areas of muscle biology:
Dobi, KC, Halfon MS, Baylies MK., 2014 Whole-genome analysis of muscle founder cells implicates the chromatin regulator Sin3a in muscle identity. Cell Reports. 2014 Jul 30. pii: S2211-1247(14)00572-5. PMID:25088419. PMCID: PMC – in process.
Bothe, I., Deng, S., Baylies MK 2014 PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site. Development. 141(11):2289-301. PMID: 24821989. PMCID: PMC4034421
Folker, E., Schulman, V., Baylies MK. 2014 Translocating myonuclei have distinct leading and lagging edges which require Kinesin and Dynein. Development. 141(2):355-66. doi: 10.1242/dev.095612. Epub 2013 Dec 11. PMID: 24335254. PMCID: PMC3879816
Folker, E., Schulman, V., Baylies MK. 2012 Muscle length and myonuclear position are independently regulated by distinct Dynein pathways. Development. 139(20):3827-37. PMID: 22951643. PMCID:PMC3445310
Nowak SJ, Aihara H, Gonzalez K, Nibu Y, Baylies MK. 2012. Akirin links Twist-regulated transcription with Brahman chromatin remodeling complex during embryogenesis. PloS Genetics: 8, e1002547, 2012. PMID:22396663. PMCID: PMC3291577
Metzger T, Gache V, Xu M, Cadot B, Folker ES, Richardson BE, Gomes ER, Baylies MK. 2012 MAP and Kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature. 484:120-124. PMID: 22425998. PMCID: PMC3321085
Developed a Drosophila model for metastasis in alveolar rhabdomyosarcoma, a type of soft tissue cancer most often seen in children
Demonstrated that properly placed nuclei are critical for healthy muscle function
Described how nuclear polarization occurs during myonuclear movement in vivo
Completed the first spatial and temporal characterization of an F-actin structure that forms at the myoblast fusion site
Identified transcription factors and chromatin regulators that are critical for muscle identity
Identified 3-D arrangement of myoblasts that occur during muscle specification and morphogenesis
Discovered signal transduction pathways (Notch, Wnt, BMP, and RTK) and transcription factors that are critical for muscle identity
President of the Society for Muscle Development (2009-2013)
Frederick Adler Chair for Junior Faculty (1997-2003)