B6.012 - Early Development of Skeletal System Flashcards
ectoderm derivatives
neuraal crest originating from neural tube
mesoderm derivatives
paraxial and lateral plate
where does muscle tissue originate from
mesodermal germ layer
where do skeletal muscle, smooth muscle and cardiac muscle originate from
skeletal - paraxial mesoderm
smooth - splanchnic/visceral LPM
Cardiac - splanchnic/visceral LPM
describe skeletal muscle early development
skeletal muscle arises from somitomeres and somites (paraxial mesoderm derivatives).
describe development of skeletal muscle in the head
The head muscle comes from 7 somitomeres in occipital region, because it forms so quickly it doesn’t undergo epithelialization like body wall and limb muscle
describe development of skeletal muscle in the body wall and limbs
somitomeres undergo epithelialization to form balls of epithelial cells with cavities (somites) extending from occipital region to tail bud
what do each paraxial mesoderm derived somite form
sclerotome (ribs, vertebrae, rib cartilage) myotome (muscles of back and body wall) dermatome (connective tissue of dermis of back) ventrolateral cells (most of musculature for body wall)
describe formation of the sclerotome and dermatome
ventral region of somite becomes mesenchymal again to form sclerotome dorsal region of somite becomes dermatome and 2 muscle forming regions (Dorso-medial and ventro-lateral); cells migrate ventrally

describe the formation of the dermamyotome
its formed from migrating DM and VL muscle cells migrating ventral to dermatome to form the myotome

describe formation of skeletal muscles
myotome cells form muscles of the back, shoulder girdle and intercostal m.
Subset of ventro-lateral muscle cells migrate into the lateral plate mesoderm (parietal layer) to form the infrahyoid, abdominal wall and limb muscles
what muscles are formed by the ventro lateral muscle cells that migrate to the lateral plate mesoderm
infrahyoid, abdominal wall, limb muscles
what is the LSF (Lateral somitic fronteir)
separates 2 domains of muscle precursor cells (based on origin) and defines molecular signaling
what are the 2 domains separated by the LSF
primaxial and abaxial
what is the primaxial domain
region around the neural tube; contains only somite (paraxial mesoderm) derived cells signaing from neural tube and notochord
what is the abaxial domain
parietal layer of LPM plus somite cells from ventrolateral regions of myotome that migrated across LSF (signaling from LPM)
describe skeletal muscle formation from myoblasts
muscle precursors (myoblasts) fuse and form long, multinucleated muscle (myo) fibers, wrapped in CT (endomysium)
myofibrils appear in cytoplasm, cross striations appear at end of 3rd month
bundles of myofibers wrapped in CT (epimysium) are called fascicles, partitions of CT (perimysium) form septa
CT contains blood vessels and nerves
describe cardiac muscle formation
in the 4th week
develops from the lateral plate (splanchnic) mesoderm (mesenchyme) surrounding endothelial heart tube
myoblasts adhere to each other by special attachments that develop into intercalated discs, growth of myofibers occurs by formation of new myofilaments
unlike skeletal muscle myoblasts DO NOT FUSE
describe myofibers
mono or binucleated
some bundles of muscle cells with irregularly distributed (fewer) myofibrils and larger diameters form purkinje fibers
describe smooth muscle formation
multiple origins: LPM, SMC of some blood vessels
proepicardial cells and neural crest: SMC of coronary arteries
surrounding LPM (splanchnic) SMC of wall of gut and its derivatives
ectoderm: SMC of pupil sphincter and dilator muscles, myoepithelial cells in mammary and sweat glands
describe differentiation of smooth muscle cell formation
differentiation of mesenchymal cells begins with development of elongated nuclei in spindle shaped byoblasts
myoblasts do NOT fuse and remain mononucleated
in later development more SMC are formed by division of existing myoblats
filamentous but non sarcomeric contractile elements develop in cytoplasm
smooth muscle fibers develop into sheets or bundles
describe the origin of tendons
axial - dorsolateral sclerotome (PA mesoderm) derivatives, lie adjacent to myotomes and ant. & post. somite borders
limb - lateral plate mesoderm and dorsolateral sclerotome
describe the origin of ligaments
scleraxis is marker
exact origin from somite not clear
describe deep fasica origins
originates from mesenchymal (mesodermal) undifferentiated CT
present in embryo from week 21
runs parallel to skin below subcutaneous adipose tissue, projections extend superficially to organize adipose tissue, and deeply to embed muscle
describe molecular regaulation of tendon development
regulated by SCLERAXIS transcription factor
describe muscle development molecular regulation
regulated by MyoD and MYF5
ventrolateral muscle expression of MyoD regulated by LPM: BMP4 and FGF
ectoderm: WNT
dorsomedial muslce expression of MYF5 regulated by: ectoderm: BMP4
Neural tube: WNT (induced by BMP4)
neural tube floor plate and notochord: SHH (at low levels)
describe patterning of muscles
controlled by connective tissue (produced by fibroblasts) into which the myoblasts migrate
sources are:
head - neural crest
occipital and cervical region - somotic mesoderm
body wall and limbs - LPM (parietal)
describe limb growth and development
weeks 4-8
limbs, including shoulder and pelvic girdles comprise the appendicular skeleton
limb buds visible at end of 4th week of development
forelimbs before hindlimbs
limb bud components
a. mesenchymal core (LPM - parietal/somatic layer) will form bones and connective tissue
b. overlying cuboudal ectoderm (part of which will form the apical ectodermal ridge)
with is the apical ectodermal ridge
extoderm at distal border of each limb that is thickened
AER induces adjacent mesenchyme to remain undifferentiated
AER has a role in forming proximal distal axis
describe limb development at 6 weeks
the terminal portion of limb buds flatten to form hand and foot plates and become separated from proximal segment by a circular constriction
describe formation of hyaline cartilage models
as limb grows - cells furthest from AER differentiate into chondrocytes forming cartilage models that precede bone
describe limb development at 7-8 weeks
each limb has 3 components
- stylopod (forms humerus and femur, proximal)
- zeugopod (forms radius/ulna, tibia/fibula)
- autopod (will form carpals, metacarpals, tarsals, metatarsals, distal)
describe limb rotation in the 7th week
upper - 90 degrees laterally
lower - 90 degrees medially
decribe digit formation
programmed cell death (apoptosis) in AER separates ridge into 5 parts
digit outgrowht continues under influence of 5 ectodermal ridges
mesenchyme condense to form 5 carticaginous digital arrays
apoptosis occurs in between digital arrays
what is brachydactyly, syndactyly, polydactyly, ectrodactyly, cleft hand/foot due to

what types of joints form between weeks 6-8
joints formed in cartilagenous condensations
chondrogenesis is arrested, joint interzone ins induced
- fibrous joints (sutures of skull)
- cartilagenous joints (pubic symphysis)
- synovial joints (knee)
describe synovial joint formation
cells in interzone increase in number/density and form dense fibrous tissue
fibrous tissue forms articular cartilage, synovial membranes, menisci and ligaments in joint capsule
cell death creats joint cavity
surrounding mesenchymal cells differentiate into a joint capsule
describe innervation of joints
a joint will be innervated by the same nerves that innervate the attached muscles and overlying skin. in addition to the fibers carrying proprioceptive information there are abudnant pain fibers in the joint
what is arthrogryposis
congenital join contractures
what is this

arthrogryposis - congenital joint contractrues
describe limb muscle development
formation of myotomes of somites
begin to form in 7th week
condensation of mesenchyme near base of limb buds forms (derivative of dorsolateral cells of somites that migrate)
initially segmented according to somite origin; but single muscle eventually is formed frommore than 1 segment
limb muslce patterning basedon connective tissue derived from LPM
describe flexor v extensor limb muslce formation from myotomes
with elongation of limb buds the muscle plits into flexor and extensor compartments from abaxial origin
what is are poland sequence and prune belly syndrome

what are muscular dystrophies
inherited muscle diseases that cause progressive muscular wasting and weakness
some caused by mutations in gene for dystrophin on X chromosome
what is dystrophin
cytoplasmic protein
forms protein comlex linking contractile elements to cell membrane
maintains cell structure of myocytes and enables them to contract
replaced by fibrous tissue
what are duchenne and becker MD

describe motor innervation of the developming musculature
due to vertebral level from which muscle cells originate
limb m. innervated by primary ventral rami of spinal nerves from its spinal segment which divides to form dorsal and ventral branches to compartments
branches unite to form larger dorsal and ventral nerves
contact between nerve and muscle cells is necessary for functional differentiation
describe sensory innervation of developing limb musculature
by spinal nerves, reflects the embryological origin and innervation of skin dermatomes (NOT somite dermatome)
dermatome pattern changes with growht and rotation of extremities but retains segmental pattern
describe blood supply to limbs
limb buds are supplied by branches of the intersegmental arteries arising from aorta
primary axial artery and its branches form oin limbs, and vascular patterning progresses via angiogenesis to form vessesl of uppand lower limbs
describe molecular regulatino of proximal distal limb development
limb outgrowth from body wall is initiated by FGF10 from LPM
BMPs in ventral ectoderm induce formation of AER distally
Radical Fringe in dorsal limb ectoderm restricts AER to distal limb tip. Results in induction of SER 2
SER 2 expressed at border (assisted by ENGRAILED-1) establishes AER, whith then expresses FGF4 and 8 - maintain progress zone/undifferentiated zone of proliferating mesenchyme near AER
describe patterning of 3 limb segments in the proximal to distal axis
depends on relative distance from signals
AER expresses FGF4 and 8 - maintain undifferentiated zone
cells further from AER respond to retinoic acid signaling from flank mesoderm
where 2 cell groups meet is differentiation front
describe molecular regulation of anterior-posterior limb development
regulated by zone of polarizing activity (ZPA): a cluster of mesenchymal cells at posterior border of limb near AER
ZPA produces retinoic acid whihc leads to expression of sonic the hedgehog which contributes to specification of posterior in AP axis (pinkie finger)
As limbs grow ZPA moves distally in proximity to posterior border of AER
dysregulation of anterior to posterior limb development is mediated by
abnormal expression of SHH by ZPA “misplaced” to anterior border (along wiht normal ZPA in posterior border) = duplication of the ZPA and SHH signaling
this results in mirror duplication of posterior limb structures (little fingers)
describe the mediation of patterning of 3 limb segments: anterior to posterior axis
HOX gene expression in limb (overlapping patterns) correspond to stylopod, zeugopod and autopod
HOX gene expression dependent on combinatorial expression of other genes
Types and shapes of bones in limb also regulated by HOX genes
molecular regulation of doral ventral limb development
BMPs expressed in ventral ectoderm, which induce transcription factor EN1
WNT7 is expressed in dorsal ectoderm, leads to induction of LMX1 in dorsal mesechyme
EN1 represses WNT7a, restricting it to dorsal limb ectoderm
Thus - BMPs and Wnt7a act antagonistically
WNT7a maintains SHH and ZPA (thus Wnt7a is indirecting involved in AP patterning)
what is amelia, meromelia, phocomelia and micromelia
amelia - complete absence of upper/or lower limbs
meromelia - partial absence of limbs
phocomelia - long bones absent; rudimentary hands/feet attached to trunk (subset of meromelia)
micromelia - all segments of limb present, but short
what are teeth
arise from interactions between oral epithelium and underlying neural crest cderived mesenchyme
NOT bones
harder than bones due to dentine
compare and contrast bones and teeth

toothe development
3 months
buds for permanent teeth form and lie on lingual aspect of milk teeth
buds remain dormant until about 6 years
milk teeth are lost as permanent teeth grow, root overlying deciduous tooth is resorbed by osteoclasts