The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution. These notes introduce the topic of early molecular development of the musculoskeletal system, later molecular develoment is covered on pages describing specific tissue development.
Early Somites Stage10
Somites Stage 11
The intraembryonic mesoderm can be broken into paraxial, intermediate and lateral mesoderm relative to its midline position. During the 3rd week the paraxial mesoderm forms into somites. Somites appear bilaterally as pairs at the same time and form earliest at the cranial (rostral,brain) end of the neural groove and add sequentially at the caudal end. This addition occurs so regularly that embryos are staged according to the number of somites that are present. Different regions of the somite differentiate into dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes.
Differentiation/determination of mesoderm into muscle cells is thought to involve a family of basic Helix-Loop-Helix transcription factors, the first of which discovered was MyoD1. (see OMIM entry). This transcription factor needs to form a dimer to be active and is maintained in an inactive state by binding of Id (see OMIM entry).
Page Links: Introduction | Some Recent Findings | Limb Molecular Development | Muscle Molecular Development | Cartilage Molecular Development | Bone Molecular Development | | Terms | References | Glossary | Development Terms
For more details about Limb development see Limb Development page and for specific information about factors involved in limb patterning see the general Molecular Development page or use the links listed below.
Ten Berge D, Brugmann SA, Helms JA, Nusse R. Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development. Development. 2008 Oct;135(19):3247-57.
"We have identified target genes that are synergistically regulated by Wnts and FGFs, and show how these factors actively suppress differentiation and promote growth. Finally, we show how the spatial restriction of Wnt and FGF signals to the limb ectoderm, and to a specialized region of it, the apical ectodermal ridge, controls the distribution of cell behaviors within the growing limb, and guides the proper spatial organization of the differentiating tissues."
Limb Specification (Fore- Hind-)
Limb Patterning- Axes
Limb Patterning- Axes
For more details about skeletal muscle development see Skeletal Muscle page and for specific information about the factors involved in muscle see the general Molecular Development page or use the links listed below. Note smooth and cardiac muscle molecular development are covered in oter notes.
The first key to understanding muscle development came from the discovery of a gene that when introduced into fibroblast cells was able to transform them into muscle. This gene was designated myogenic determining factor number one (MyoD1). MyoD1 is a basic-helix loop helix transcription factor that binds DNA as a heterodimer. (More? Molecular Factors - MyoD)
Subsequently a family of muscle "determining" factors have been identified and the issue of determination versus differentiation were initially contentious issues. The links below are to OMIM entries for specific factors.
For more details about cartilage development see Cartilage page and for specific information about the factors involved in muscle see the general Molecular Development page or use the links listed below.
Hyaluronan receptor (CD44) - cell membrane glycoprotein, expression occurs at the time of reduction of intercellular spaces at sites prior to cartilage deposition. Signaling through this receptor pathway affects both chondrocyte survival and apoptotis.
Links: OMIM - CD44
Dicer - 21 nucleotide small regulatory RNA required in RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression.
For more details about bone development see Bone page and for specific information about the factors involved in bone development see the general Molecular Development page or use the links listed below.
The transcription factor Core Binding Factor 1 (Cbfa1) plays an essential role in osteoblast differentiation, bone formation, matrix production and mineralization.
Links to related WWW sites with Histological images for Skeleton/ Muscle/ Connective Tissue system.
Note that all internet links change with time if link does not work use text shown to search WWW. (Also see All systems)