The laryngeal muscle of the anuran Xenopus laevis undergoes a complete switch from a mix of fast and slow twitch muscle fibers to all fast twitch fibers in response to androgen treatment. The proposed experiments will investigate the role of myogenic stem cells (myoblasts) in this androgen response. Mitotic cells, including myoblasts, are first depleted from larynges by the use of anti-neoplastic drugs and radiation. Myoblasts will then be isolated from larynges of animals expressing green fluorescent protein and transplanted back into irradiated larynges in order to determine their ability to rescue the response to androgen. Further experiments will determine whether myoblasts are the target of androgen by rendering larynges androgen insensitive by means of a dominant negative androgen receptor (dnAR). Myoblasts from wild-type larynges will then be transplanted into those expressing the dnAR in order to determine their ability to rescue the androgen response.
The final aim of the application is to determine the androgen responsive target genes responsible for fiber type switching. ? ?
Nasipak, Brian; Kelley, Darcy B (2012) Developing laryngeal muscle of Xenopus laevis as a model system: androgen-driven myogenesis controls fiber type transformation. Dev Neurobiol 72:664-75 |
Nasipak, Brian T; Kelley, Darcy B (2008) The genome of the diploid anuran Xenopus tropicalis contains a novel array of sarcoplasmic myosin heavy chain genes expressed in larval muscle and larynx. Dev Genes Evol 218:389-97 |