Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>

Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>

Bibliographic Details
Main Author: Zhang, Hong
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2009
Subjects:
Biomedical Research
<i>Ski</i>
knockout mice
muscle development
progenitor
hypaxial muscle
Pax3
Pax7
Met
myogenic regulatory factors
myoblast
Myog
MHC
MyoD
MEF2
Six1
Eya3
Dach
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1226938149
id ndltd-OhioLink-oai-etd.ohiolink.edu-case1226938149
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case12269381492021-08-03T05:32:55Z Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i> Zhang, Hong Biomedical Research <i>Ski</i> knockout mice muscle development progenitor hypaxial muscle Pax3 Pax7 Met myogenic regulatory factors myoblast Myog MHC MyoD MEF2 Six1 Eya3 Dach <i>Ski</i> is the most studied member of a family of proteins all sharing a conserved Dachshund homology domain. It has been implicated in oncogenic transformation, myogenic conversion of avian embryo fibroblasts and also many aspects of vertebrate development, especially myogenesis. <i>Ski</i>-/- mice exhibit severe defects in skeletal muscle and die at birth, yet little is know about either the underlying mechanisms or the role of <i>Ski</i> in adult muscle regeneration. In these studies, I used <i>Ski</i> knockout mice and C2C12 myoblast cultures to address these issues, respectively. Detailed analysis of <i>Ski</i>-/- embryos revealed dramatically reduced hypaxial muscles but less affected epaxial muscles. The reduced number of myogenic regulatory factor positive cells in <i>Ski</i>-/- mice suggested an insufficient myogenic cell pool to support muscle formation. However, both the dermomyotomal hypaxial progenitors and myotomal epaxial progenitors formed and committed to myogenic fate appropriately. The hypaxial muscle defect in <i>Ski</i>-/- mice was not caused by abnormal proliferation, terminal differentiation or apoptosis of the myogenic cells either, but due to impaired migration of embryonic hypaxial progenitors. Surprisingly, the normal distribution of fetal/postnatal myogenic progenitors in <i>Ski</i>-/- mice suggested different effects of <i>Ski</i> on the behaviors of embryonic and fetal/postnatal myogenic progenitors. In addition, although not affecting the terminal differentiation of embryonic myogenic cells, <i>Ski</i> was necessary for that of adult satellite-cell derived C2C12 myoblasts as evidenced by impaired myotube formation and reduced induction of genes essential for myogenic differentiation in the absence of Ski. This function was mainly mediated by Ski’s ability to form a complex with Six1 and Eya3 and activate <i>Myog</i> transcription through a MEF3 site. It is important in the future to further study mechanisms underlying the contrasting effects of <i>Ski</i> on embryonic, fetal and adult muscle development, to investigate how the association of Ski with Six1/Eya3 is triggered upon differentiation and to identify the transcriptional machinery mediates Ski’s action. The data presented here not only add a new aspect to the understanding of myogenic progenitor migration and hypaxial muscle development but also provide a starting point to achieve the regulation of muscle formation and regeneration through the action of <i>Ski</i>. 2009 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1226938149 http://rave.ohiolink.edu/etdc/view?acc_num=case1226938149 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
<i>Ski</i>
knockout mice
muscle development
progenitor
hypaxial muscle
Pax3
Pax7
Met
myogenic regulatory factors
myoblast
Myog
MHC
MyoD
MEF2
Six1
Eya3
Dach
spellingShingle Biomedical Research
<i>Ski</i>
knockout mice
muscle development
progenitor
hypaxial muscle
Pax3
Pax7
Met
myogenic regulatory factors
myoblast
Myog
MHC
MyoD
MEF2
Six1
Eya3
Dach
Zhang, Hong
Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
author Zhang, Hong
author_facet Zhang, Hong
author_sort Zhang, Hong
title Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
title_short Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
title_full Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
title_fullStr Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
title_full_unstemmed Regulation of Skeletal Muscle Development And Differentiation by <i>Ski</i>
title_sort regulation of skeletal muscle development and differentiation by <i>ski</i>
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2009
url http://rave.ohiolink.edu/etdc/view?acc_num=case1226938149
work_keys_str_mv AT zhanghong regulationofskeletalmuscledevelopmentanddifferentiationbyiskii
_version_ 1719421579484463104

Similar Items