Muscle development: forming the head and trunk muscles.
The morphological events forming the body's musculature are sensitive to genetic and environmental perturbations with high incidence of congenital myopathies, muscular dystrophies and degenerations. Pattern formation generates branching series of states in the genetic regulatory network. Different states of the network specify pre-myogenic progenitor cells in the head and trunk. These progenitors reveal their myogenic nature by the subsequent onset of expression of the master switch gene MyoD and/or Myf5. Once initiated, the myogenic progression that ultimately forms mature muscle appears to be quite similar in head and trunk skeletal muscle. Several genes that are essential in specifying pre-myogenic progenitors in the trunk are known. Pax3, Lbx1, and a number of other homeobox transcription factors are essential in specifying pre-myogenic progenitors in the dermomyotome, from which the epaxial and hypaxial myoblasts, which express myogenic regulatory factors (MRFs), emerge. The proteins involved in specifying pre-myogenic progenitors in the head are just beginning to be discovered and appear to be distinct from those in the trunk. The homeobox gene Pitx2, the T-box gene Tbx1, and the bHLH genes Tcf21 and Msc encode transcription factors that play roles in specifying progenitor cells that will give rise to branchiomeric muscles of the head. Pitx2 is expressed well before the onset of myogenic progression in the first branchial arch (BA) mesodermal core and is essential for the formation of first BA derived muscle groups. Anterior-posterior patterning events that occur during gastrulation appear to initiate the Pitx2 expression domain in the cephalic and BA mesoderm. Pitx2 therefore contributes to the establishment of network states, or kernels, that specify pre-myogenic progenitors for extraocular and mastication muscles. A detailed understanding of the molecular mechanisms that regulate head muscle specification and formation provides the foundation for understanding congenital myopathies. Current technology and mouse model systems help to elucidate the molecular basis on etiology and repair of muscular degenerative diseases.
Shih
Hung Ping
HP
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Gross
Michael K
MK
Kioussi
Chrissa
C
D000818:Animals; D006257:Head / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008410:Masticatory Muscles / Q000196:embryology; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D009801:Oculomotor Muscles / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2