Development of the musculoskeletal system Flashcards
What embryonic germ layer is skeletal muscle derived from?
Paraxial mesoderm
Where are the epaxial muscles located and what do they form upon maturation?
They are dorsal to the transverse processes and form the intrinsic muscles of the back
What line do myotomes originate from?
Somites
Formed by the cells at the ventrolateral lip (VLL) of the prospective myotome region and by cells from the dorsomedial lip (DML)
What portion of the mesoderm do VLL contribute cells to?
Cells at the ventrolateral lip contributes cells to both the primaxial and abaxial domains of the mesoderm
What portion of the mesoderm do DML contribute cells to?
Cells at the dorsomedial lip contribute to the primaxial domain of the mesoderm (also includes sclerotome and dermatome cells)
What cells does the primaxial domain contain? What does this domain form?
Cells from the paraxial mesoderm.
Forms muscles of the back, shoulder girdle (rhomboids, levator scapulae, and latissimus dorsi), and intercostals
What cells form dermis on the back (from dermatomes), vertebrae, and bony parts of the ribs (from sclerotome)?
Paraxial cells
What does the abaxial domain form?
Limb and abdominal wall (obliques and transversus abdominus muscles)
What do abaxial cells form?
The dermis in the body wall (from lateral plate mesoderm) and rib cartilages (from sclerotome cells that migrate across the lateral somitic frontier)
Where do migrating muscle cells receive innervation from?
Their spinal segments of origin - migrating muscle cells carry these spinal nerves with them as they migrate
What molecular regulation is important for the formation of skeletal muscle?
WNT, MyoD, BMP4 with low SHH
Describe the patterning of the muscles in the head
Head musculature formed by somitomeres - tongue, eye (except those of the iris = pupillary muscles = derived from the optic cup) and pharyngeal arches.
Muscles in the head are patterned by connective tissue that is formed by neural crest
Describe the patterning of the muscles of the limb:
Limb muscles formed by VLL cells: patterned by connective tissue formed by lateral plate mesoderm regulated by MyoD genes (transcription factor)
Describe the formation of cardiac muscle:
Derived from visceral mesoderm surrounding heart tube
Intercalated discs
Purkinje fibers
Describe the formation of smooth muscle:
Embryonic derivative of visceral layer of lateral plate mesoderm, some neural crest cells for sphincter and dilater
Molecular commitment — SRF, MRTFs
Paraxial mesoderm forms ________ along the spinal cord and somitomeres in the head.
Somites
What are the three components of somites?
Dermatome (skin)
Myotome (muscle)
Sclerotome (bone)
What is mesenchyme tissue?
Mesenchyme tissue = any loose connective tissue regardless of origin (i.e. neural crest cells)
List the parts of the neurocranium:
Membranous (membranes - intramembranous ossification)
Condrocranium
Sutures
List the parts of the viscerocranium
Face
Mostly from the frontonasal prominence and the 1st and 2nd pharyngeal arches - neural crest cells
1st arch = maxilla, mandible, malleus, incus
2nd arch - stapes, part of hyoid bone
When do the limb buds form?
During the 4th and 5th weeks
What specifies the location and type (forelilmb/hindlimb) of limb budding?
HOX genes location
TBX5 specifies forelimb structures
TBX4 specifies hindlimb structures
AER
Apical ectodermal ridge - proximodistal growth - FGF’s maintain a rapidly proliferating population of cells adjacent to the ridge - the progress zone
ZPA
Zone of polarizing activity - cranial to caudal (anterior-posterior) patterning, thumb to little finger - SHH and retinoic acid - morphogens
How do the digits separate during development?
Cell death in ridge
What determines bone patterning
HOX genes
What clinical issues are associated with limb development?
Amelia - no limbs
Meromelia - short limbs
Talidomide - limb defects, now an anticancer and anti AIDS drug so we are seeing these limb defects again
syndactyly - fused digits
brachydactylly - short digits
What is the vertebral column derived from?
Somites (slerotome) and notochord (nucleus pulposus)
Caudal part of one clerotome fuses with cranial part of another - intersegmental so that muscles bridge the vertebra to act on them - resegmentation
What are the two major parts of the skull?
The viscerocranium (face)/Neurocranium(flat bones of the skull from paraxial mesoderm)
What do the hypaxia muscles form?
Muscles in the body wall
Anywhere there is segmentation in the embryo there are ____ genes:
HOX
What upper limb muscles are derived from the VLL that migrate across the lateral somitic frontier?
All distal limb muscles
What muscles do the primaxial cells give rise to?
The extrinsic and intrinsic back muscles
What gives rise to the spinal ganglia?
The neural crest cells (ganglia composed of cell bodies)
What do abaxial/sclerotome form when they cross the lateral somitic frontier?
The ribs
What is the relationship between homebox and HOX genes?
All HOX are homeobox genes, not all homeobox are HOX
How do vertebrae form from somites?
The caudal half of one fuses with the cranial half of another.
This process is called resegmentation
What cell population is responsible form forming the neurocranial region?
Paraxial mesoderm
What cell population is responsible for forming the viscerocranial region?
Neural crest cells
What cell population is responsible for forming the chordal chondrocranium?
The paraxial mesoderm
What cell population is responsible for forming the viscero chondrocranium?
Neural crest cells
What causes craniusynostosis and achondroplasia?
Mutations in the fibroblast growth factor receptors (FGFRs)
What is SALL4?
Transcription factor that regulates FGF. Drugs that interfere with SALL4 during embryogenesis cause birth defects where the fetus has shortened limbs.
What gene misregulation causes polydactyly?
SHH
What is responsible form the location of limb bud formation?
The HOX genes
FGF 10 is expressed in the lateral mesoderm that induces limb bud growth
What growth regulation factors does the apical ectrodermal ridge secrete?
FGF4 and FGF8
The flank mesoderm initiates limb outgrowth and causes the AER
Where and what is the zone of polarizing activity?
The ZPA secretes SHH and specifies anterior-posterior patterning (i.e. thumb to little finger)
