Using the Xenopus Model to Elucidate the Functional Roles of Leiomodin3 and Tropomodulin4 (Tmod4) During Skeletal Muscle Development

Persistent Link:
http://hdl.handle.net/10150/311689
Title:
Using the Xenopus Model to Elucidate the Functional Roles of Leiomodin3 and Tropomodulin4 (Tmod4) During Skeletal Muscle Development
Author:
Nworu, Chinedu Uzoma
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Having an in vivo model of development that develops quickly and efficiently is important for investigators to elucidate the critical steps, components and signaling pathways involved in building a myofibril; hence a compliant in vivo model would provide a pivotal foundation for deciphering muscle disease mechanisms as well as the development of myopathy-related therapeutics. Here, we take advantage of a relatively quick, cost effective, and molecularly pliable developmental model system in the Xenopus laevis (frog) embryo and establish it as an in vivo model to study the roles of sarcomeric proteins during de novo myofibrillogenesis.Using the Xenopus model, we elucidated the functional roles of Leiomodin3 (Lmod3) and Tropomodulin 4 (Tmod4) during de novo skeletal myofibrillogenesis. Tmods have been demonstrated to contribute to thin filament length uniformity by regulating both elongation and depolymerization of actin-thin filaments' pointed-ends. Lmods, which are structurally related to Tmod proteins also localize to actin filament pointed-ends. In situ hybridization studies demonstrated that of their respective families, only tmod4 and lmod3 transcripts were expressed at high levels in skeletal muscle from the earliest stages of development. When reducing their protein levels via morpholino (MO) treatment, thin filament regulation and sarcomere assembly were compromised. Surprisingly, alternate rescues (i.e., lmod3 mRNA co-injected with Tmod4 MO and vice versa) partially restored myofibril structure and actin-thin filament organization. Thus, our results not only indicate that both Tmod4 and Lmod3 are critical for myofibrillogenesis during Xenopus skeletal muscle development, but also revealed that they may share redundant functions during skeletal muscle thin filament assembly.
Type:
text; Electronic Dissertation
Keywords:
sarcomere; skeletal muscle development; thin filament regulation; Tmod; Xenopus; Cell Biology & Anatomy; Lmod
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Cell Biology & Anatomy
Degree Grantor:
University of Arizona
Advisor:
Gregorio, Carol C.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleUsing the Xenopus Model to Elucidate the Functional Roles of Leiomodin3 and Tropomodulin4 (Tmod4) During Skeletal Muscle Developmenten_US
dc.creatorNworu, Chinedu Uzomaen_US
dc.contributor.authorNworu, Chinedu Uzomaen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHaving an in vivo model of development that develops quickly and efficiently is important for investigators to elucidate the critical steps, components and signaling pathways involved in building a myofibril; hence a compliant in vivo model would provide a pivotal foundation for deciphering muscle disease mechanisms as well as the development of myopathy-related therapeutics. Here, we take advantage of a relatively quick, cost effective, and molecularly pliable developmental model system in the Xenopus laevis (frog) embryo and establish it as an in vivo model to study the roles of sarcomeric proteins during de novo myofibrillogenesis.Using the Xenopus model, we elucidated the functional roles of Leiomodin3 (Lmod3) and Tropomodulin 4 (Tmod4) during de novo skeletal myofibrillogenesis. Tmods have been demonstrated to contribute to thin filament length uniformity by regulating both elongation and depolymerization of actin-thin filaments' pointed-ends. Lmods, which are structurally related to Tmod proteins also localize to actin filament pointed-ends. In situ hybridization studies demonstrated that of their respective families, only tmod4 and lmod3 transcripts were expressed at high levels in skeletal muscle from the earliest stages of development. When reducing their protein levels via morpholino (MO) treatment, thin filament regulation and sarcomere assembly were compromised. Surprisingly, alternate rescues (i.e., lmod3 mRNA co-injected with Tmod4 MO and vice versa) partially restored myofibril structure and actin-thin filament organization. Thus, our results not only indicate that both Tmod4 and Lmod3 are critical for myofibrillogenesis during Xenopus skeletal muscle development, but also revealed that they may share redundant functions during skeletal muscle thin filament assembly.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectsarcomereen_US
dc.subjectskeletal muscle developmenten_US
dc.subjectthin filament regulationen_US
dc.subjectTmoden_US
dc.subjectXenopusen_US
dc.subjectCell Biology & Anatomyen_US
dc.subjectLmoden_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineCell Biology & Anatomyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGregorio, Carol C.en_US
dc.contributor.committeememberGregorio, Carol C.en_US
dc.contributor.committeememberKrieg, Paul A.en_US
dc.contributor.committeememberElliott, David A.en_US
dc.contributor.committeememberLybarger, Lonnieen_US
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