B6.012 - Early Development of Skeletal System Flashcards Preview

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Flashcards in B6.012 - Early Development of Skeletal System Deck (60):

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

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describe the formation of the dermamyotome

its formed from migrating DM and VL muscle cells migrating ventral to dermatome to form the myotome 

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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

1. stylopod (forms humerus and femur, proximal)

2. zeugopod (forms radius/ulna, tibia/fibula)

3. 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

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what types of joints form between weeks 6-8

joints formed in cartilagenous condensations

chondrogenesis is arrested, joint interzone ins induced

1. fibrous joints (sutures of skull)

2. cartilagenous joints (pubic symphysis)

3. 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

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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

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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

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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

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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