Embryology of Bone and Muscle Flashcards
Embryonic connective tisse
Mesenchyme
Mesenchyme is derived from _______ and _______
mesoderm and neural crest
defines axes, mechanical role in folding process, signaling role in formation of neural groove/tube, somites (indirectly) and musculoskeletal system (via Shh)
contributes to vertebral bodies and intervertebral discs
Notochord
_______ induces overlying ectoderm to invaginate –> neural groove and tube
notochord
Neural tube induces formation of _____/_____ from paraxial mesoderm
vertebrae/somites
clusters of mesodermal tissue that condense segmentally in rostral to caudal progression. They are derived from paraxial mesoderm.
Somites (somitomeres)
Somitomeres –> Somites
Compact and bound by epithelium = somites
Pairs 1-7 do not compact –> contribute to formation of head and neck
Mesodermal cells from somites migrate and give rise to
Dermomyotome –> dermatomes and myotomes
Sclerotome –> bone and cartilage
Membranous bone formation
Mesenchyme condenses into a very vascular CT. Mesenchymal cells produce matrix containing collagen fibers. Cells differentiate into osteoblasts and begin to lay down mineralized bone matrix, typical in the formation of flat bones (skull).
Endochondral bone formation
Mesenchymal cells differentiate into chondroblasts –> hyaline cartilage model of the (long) bone. Matrix calcifies around the periphery of the shaft. Interiorly, some cells differentiate into osteoblasts and begin to lay down mineralized bony matrix. —Primary ossification center.
Blood vessels invade the diaphysis and stimulate ossification. The diaphysis grows in length toward the ends of the bone. Later, secondary ossification centers form in the ends (epiphyses). The epiphyses grow toward the shaft, leaving a region of hyaline cartilage, the epiphyseal (growth) plate between. Growth of the long bone stops when the cartilage plate has completely ossified.
Timing of ossification centers for long bones
Primary oss centers at week 8 in certain order
Nearly all have primaries at birth
Most secondary centers appear after birth (epiphysis)
Joint formation (overall)
Loose mesenchyme between cartilage models differentiates into fibrous tissue or fibrocartilage. Surrounded by perichondrium .
Synovial joint formation
In synovial joints, programmed cell death (apoptosis) results in joint cavity between adjacent cartilage models. Perichondrium persists as joint capsule, lining differentiates into synovial membrane. Hyaline cartilage persists on articular surfaces.
Marfan Syndrome
Connective tissue disorder - excessive long bone growth
Fibrillin-1 gene mutation
Long, thin limbs
Also can affect heart, vessels, bones, eyes, lungs
Osteogenesis Imperfecta
Defect in type 1 collagen gene Autosomal recessive OR dominant Extreme bone fragility Frequent fractures Hypermobile joints
Achondroplasia
Most common form of dwarfism
Affects long bones
Autosomal dominant or spontaneous mutation of FGFR3 gene
Gigantism
Excessive growth hormone during childhood BEFORE growth plates close
Overal large size, height and organs, normal proportions
Acromegaly
Excessive growth hormone AFTER growth plates closed
Large heavy bones especially hands and feet
Congenital Hip dysplasia/dislocation
Incomplete formation of acetabulum (hip joint)
Legs held in positions that don’t match, less movement, uneven leg length
Axial skeletal system
Skull, vertebral column, ribs/sternum
Appendicular skeletal system
pectoral and pelvic girdles
limbs
Sclerotome cells migrate ________ to form sheath around ______ and ______
ventromedially,
notochord and neural tube
Resegmentation of vertebral column
Caudal part of one segment fuses with rostral part of segment below (around the artery)
i.e. In the primitive stage, the artery appears to separate one vertebra from another. In the definitive stage, the artery lies in the middle of the vertebral body.
Each sclerotome segment is divided into two parts (____ and ______) by _______
Dense caudal and loose cranial part, intersclerotomic (Von ebner’s fissure)
Formation of intervertebral discs
Mesenchyme lying between the cephalic and caudal parts of the original sclerotome segment fills the space surrounding the notochord, becomes annulus fibrosis.
Notochord becomes nucleus pulposis.
Induced by _______, sclerotome migrate dorsally around neural tube to form vertebral arch
Neural tube
Sternum formation
2 sternal bars (mesenchyme) form in midline of thoracic ventral wall - bars fuse forming cartilage model of manubrium/sternum/xiphoid - multiple ossification centers develop and fuse
Rib formation
Form from costal processes of thoracic vertebrae
continuous w/ neural arch
costovertebral synovial joints form
Spina bifida
failure of neural tube to close
occulta - tuft of hair, lumbosacral
meningocele - meninges protrude through defect
meningomyelocele - meninge/spinal cord protrude through defect
Congenital dermal sinus
form of occult spinal dysraphia
neural ectoderm fails to completely separate from surface ectoderm - spinal cord maybe tethered to skin, risk for meningitis
Klippel-Feil Syndrome (congenital brevicollis)
Congenital fusion of any of cervical vertebrae
Scoliosis common, shortened neck d/t nonsegmentation of cervical vertebra
Hemivertebra
Congenital scoliosis - only one chondrification center forms
Cervical ribs
C7 forms rudimentary rib that can compress neurovascular structures supplying upper limb (thoracic outlet syndrome)
Lumbar ribs
more common, asymptomatic
may mistake for fracture of L1 transverse process
Pectus excavatum
Concave chest, can occur with marfan/scoliosis, worsens during puberty growth spurt
d/t to poorly coordinated growth of CT during development of sternum/costal cartilages
Pectus carinatum
thoracic cage larger, hard to get normal breath (w/ exercise)
Upper limb bud appears _____
Lower limb bud appears ______
Week 4
first (day 26), day 28
Most susceptible to teratogens through end of week 8
Location of limb buds (patterning) controlled by _________
homeobox (Hox) genes
Limb bud formation
Somitic and somatic (lateral plate) mesoderm - proliferates deep to extoderm – transfoorms into mesenchyme - small protrusions appear
Upper limb bud somite levels
C5-T1
Lower limb bud somite levels
L2-S2
Thickening of the ectoderm over the distal border forms the _______ (induced by mesodermal mesenchyme)
Apical ectodermal ridge
The AER plays a major role in limb formation by _________
inducing proliferation of undifferentiated mesenchymal cells (via fibroblast growth factors) in the adjacent progress zone
Placode
region of thickened ectoderm responsible for induction of another structure or organ (i.e. AER)
Core of limb bud is ________
Outside is _______
Mesoderm, ectoderm
Limb growth and differentiation
AER secretes fibroblast growth factors that induce underlying mesenchyme to proliferate, so that the limb lengthens but the distal aspect of limb is inhibited from terminal differentiation.
Cartilage/muscle differentiation begins in the proximal part of limb and progresses in a proximal-distal direction.
Digit formation
ZPA coalesces under influence of FGFs from AER
Shh gene activationShh proteins
Signals anterior/posterior polarity
(ie. little finger vs. thumb at this point)
Limb rotation
day 50-60 (week 8)
Limbs rotate in opposite directions (thumbs laterally - elbow back, flexors anterior vs. big toe medially - knees forward, flexors posterior)
Amelia
No limbs (bilateral or unilateral)
Meromelia
partial absence of limbs
Phocomelia
Hand or foot-like appendage attached almost directly to toroo (flipper)
Polydactyly
extra digits
may be fully formed or only soft tissues
Autosomal dominant
Syndactyly
Failure of apoptosis leading to fused digits or fused bony components
Lobster claw deformity (ectrodactyly)
Absent central ray, deep cleft between digits
Autosomal dominant
Myotomes are derived from _______ in segmental arrangement.
Somites
Muscle formation: Mesenchyme differentiates into _______
spindle shaped myoblasts
Myoblasts fuse into _____ and develop ______ within their cytoplasm
myotubes
myofilaments
Myotubes fuse to form long mulitnucleated _______ that make up skeletal muscle
myofigers
skeletal muscle formation
Somitesmyotomesmesenchymemyoblastsmyotubesmultinucleated muscle fibersstriated (skeletal) muscle
As the myotome differentiates from the dermotome, it divides into the ____, _____
smaller more dorsal (epimere)
epaxial and larger
hypaxial (hypomere) divisions.
Nerve fibers from the dorsal primary ramus are associated with the _______, which develops into the deep extensors of _______ .
Nerve fibers from the dorsal primary ramus are associated with the epimere, which develops into the deep extensors of the back.
Myoblasts in the cervical region of the hypaxial division form the ______ flexors.
Myoblasts in the cervical region of the hypaxial division form the neck flexors.
EPimere - deep back- innervated by
dorsal primary rami
hypomere - trunk wall/trunk - innervated by
ventral primary rami
Limb muscles developed via _______ myoblasts in _____ and ______ compartments
hypaxial
flexor and extensors
Poland syndrome
Underdevelopment or absence of pectoralis muscles, usually unilateral, males>females, common w/ Marfan
Prune Belly Syndrome
Poor development of abdominal muscles causing skin to wrinkle
Undescended testicles and UTIs
Congenital torticollis
Sternocleidomastoid muscle on one side is spasmodic or shortened
Usually present at birth and discovered soon
May be related to small space in uterus, common w/ hip dysplasia
Smooth muscle originates from ________ of lateral plate (except ________ and _______)
splanchnic mesoderm
somatic mesoderm – vascular system
ectoderm - myoepithelial cells of mammary and sweat glands and smooth muscle of iris
Cardiac muscle originates from _________ located around __________
splanchnic mesoderm located around heart primordium
