B6.012 Early Development of the MSK System Flashcards
1
Q
what are the components of the MSK system
A
muscles connective tissue: -bone -cartilage -ligaments -tendons -fascia
2
Q
components of muscle
A
actin and myosin
collagen in endomysium
3
Q
components of bone
A
collagen and calcium
4
Q
types of cartilage
A
fibrous- in ligaments, tendons, and joint capsules
hyaline- can provide model for bone formation
both collagen
5
Q
function and components of ligaments
A
connect bones to bones, enable motion
bands of fibrous connective tissue (collagen) with dense irregular CT sheaths surrounding bundles
6
Q
function and components of tendons
A
connect muscle to bones, allow joint movement
bands of fibrous CT (collagen), no sheath
7
Q
function and components of fascia
A
attaches, stabilizes, encloses and separates muscles
allows smooth, unrestricted movement
band or sheet of fibrous connective tissue (collagen)
8
Q
origin of general muscle tissue
A
mesodermal germ layer
9
Q
origin of skeletal muscle
A
paraxial mesoderm
10
Q
origin of smooth muscle
A
splanchnic/visceral lateral plate mesoderm
11
Q
origin of mammary and sweat gland muscles
A
ectoderm
12
Q
origin of cardiac muscle
A
splanchnic/visceral LPM
13
Q
what are the derivatives of the paraxial mesoderm that develop into skeletal muscle
A
somitomeres and somites
transient paired structures
segment cranial-caudal axis
14
Q
origin of head muscles
A
7 somitomeres in occipital region
partially segments whorls of mesenchymal cells
15
Q
origin of body wall and limbs muscle
A
somitomeres that undergo epithelialization to form balls of epithelial cells with cavities (somites)
extend from occipital region to tail bud
16
Q
derivatives of the somite
A
sclerotome
myotome
dermatome
ventrolateral cells (subset)
17
Q
sclerotome
A
ribs
vertebrae
rib cartilage
18
Q
myotome
A
muscles of the back, body wall (intercostals), and some limb muscles
19
Q
dermatome
A
connective tissue of dermis of back
20
Q
ventrolateral cells (subset of myotome)
A
most of musculature for body wall (obliques, transversus abdominis) and limbs
21
Q
how is the sclerotome formed from somite
A
ventral region of somite becomes mesenchymal again to form sclerotome
22
Q
how is dermatome formed from somite
A
dorsal region of somite becomes dermatome and 2 muscle forming regions (dorsomedial and ventrolateral)
cells migrate ventrally
23
Q
what is the dermamyotome
A
formed from migrating DM and VL muscle cells migrating ventral to dermatome to form the myotome
24
Q
what happens to a subset o VL muscle cells?
A
migrate into lateral plate mesoderm (parietal layer) to form: infrahyoid, abdominal wall, and limb muscles
25
what happens to the rest of the myotome cells?
form muscles of back, shoulder girdle, and intercostals
26
what is the lateral somatic frontier (LSF)
separates 2 domains of muscle precursor cells (based on origin) into primaxial and abaxial domains
27
primaxial domain
region around neural tube
contains only somite derived cells (paraxial mesoderm)
signaling from neural tube and notocord
28
abaxial domain
parietal layer of LPM plus somite cells from VL region of myotome that migrated across LSF
signaling from LPM
29
how do skeletal muscle cells form from myoblasts?
1. myoblasts fuse and form long, multinucleated muscle fibers, wrapped in CT (endomysium)
2. myofibrils appear in cytoplasm
3. cross striations appear at the end of the 3rd month
4. bundles of myofibers wrapped in CT (epimysium) are called fascicles
5. partitions of CT (perimysium) form septa
30
function of CT layer in skeletal muscle fibers
contains blood vessels and nerves for muscle
31
when does cardiac muscle form
4th week
32
what is the origin of cardiac muscle
lateral plate (splanchnic/visceral) mesoderm surrounding epithelial heart tube
33
how do myoblasts of cardiac muscle develop
1. myoblasts adhere to each other by special attachments that develop into intercalated disks
2. growth of myofibers occurs by formation of new myofilaments
3. myoblasts DO NOT fuse like in skeletal, myofibers are mono- or bi-nucleated
34
how do purkinje fibers differ from normal cardiac muscle fibers
bundles of muscle cells with irregularly distributed myofibrils and larger cell diameters
35
origin of smooth muscle cells (SMC) of some blood vessels
LPM (splanchnic/visceral)
36
origin of SMC of coronary arteries
proepicardial cells and neural crest
37
origin of SMC of wall of gut and its derivatives
surrounding LPM (splanchnic)
38
origin of SMC of pupil sphincter and dilator muscles
ectoderm
39
origin of myoepithelial cells in mammary and sweat glands
ectoderm
40
formation of smooth muscle cells
1. differentiation of mesenchymal cells with development of elongated nuclei in spindle shaped myoblasts
2. myoblasts DO NOT fuse and remain mononucleated
3. later, more SMC are formed by division of existing myoblasts
4. filamentous but non sarcomeric contractile elements develop in cytoplasm
5. some develop into sheets or bundles
41
origin of axial tendons
dorsolateral sclerotome (PA mesoderm) derivatives, lie adjacent to myotomes at anterior and posterior somite borders
42
origin of limb tendons
LPM and dorsolateral sclerotome
43
origin of deep fascia
mesenchymal (mesodermal) undifferentiated CT
| present in embryo from week 21
44
location of deep fascia
parallel to skin below subQ adipose tissue
projections extend superficially to organize adipose
projections extend deeply to embed muscle tissue
forms networks in body
45
factors associated with tendon development
SCLERAXIS transcription factor
46
factors associated with muscle development
MyoD and MYF5
| myogenic regulatory factors
47
factors associated with VL expression of MyoD
LPM: BMP4 and FGF
ectoderm: WNT
48
factors associated with DM expression of MYF5
ectoderm: BMP4
neural tube: WNT (induced by BMP4)
neural tube floor plate and notochord: SHH (low levels)
49
what controls muscle patterning
connective tissue (produced by fibroblasts) into which myoblasts migrate
50
sources of head connective tissue
neural crest
51
sources of occipital and cervical connective tissue
somitic mesoderm
52
sources of body wall/limb connective tissue
LPM (parietal/somatic)
53
when does limb growth and development occur
weeks 4-8
54
when are limb buds visible
end of 4th week
outpocketings of VL body wall
forelimbs precede hindlimbs by 1-2 days and ongoing forelimb morphogenesis continues to precede hindlimbs
55
components of limb buds
a) mesenchymal core (LPM- parietal/somatic) forms bones and CT
b) overlying cuboidal ectoderm (forms apical ectodermal ridge)
56
what is the apical ectodermal ridge (AER)
ectoderm at distal border of each limb thickens to for AER
induces adjacent mesenchyme to remain undifferentiated
has role in forming proximal-distal axis
57
what happens to limb development at 6 weeks
terminal portion of limb buds
a) flatten to form hand and foot plates
b) become separated from proximal segment by a circular constriction
58
what are hyaline cartilage models
as limb grows, cells furthest from AER differentiate into chondrocytes and form cartilage models (6th week)
hyaline cartilage models precede bone
59
3 clear components of limbs
1. stylopod (proximal)
2. zeugopod
3. autopod (distal)
60
what happens in the 7th week of limb development
limbs develop 3 clear components
limbs rotate in opposite directions
upper: 90 degrees laterally
lower: 90 degrees medially
61
how do digits form
1. programmed cell death in AER separates ridge into 5 parts
2. digit outgrowth continues under influence of 5 ectodermal ridges
3. mesenchyme condenses to form 5 cartilaginous digital arrays
4. programmed cell death occurs between digital arrays to form digits
62
brachydactyly
shortened digits
63
syndactyly
fused soft tissue and/or bones of digits
| failure of apoptosis of interdigit mesenchyme
64
polydactyly
extra digits
| lack proper muscle connections
65
ectrodactyly
lack of central digits (cleft hand/foot)
66
cleft hand/foot
abnormal cleft between 2nd and 4th metacarpals/tarsals and soft tissues
3rd metacarpal/tarsal absent
67
overview of joint formation
weeks 6-8
joints are formed in cartilaginous condensations
chondrogenesis is arrested and a joint interzone is induced
68
3 types of joints
fibrous
cartilaginous
synovial
69
fibrous joints
joined by fibrous tissue, limited mobility
interzonal mesenchyme between bones differentiates into dense fibrous tissue
ex: sutures of skull
70
cartilaginous joints
joined by cartilage, limited mobility
interzonal mesenchyme between bones differentiated into hyaline (costochondral joints) or fibrocartilage (pubis symphysis)
71
synovial joints
common joint, most mobile
| ex: knee
72
knee joint (synovial) formation
1. cells in interzone increase in number/density and form dense fibrous tissue
2. fibrous tissue forms articular cartilage, synovial membranes, menisci and ligaments in joint capsule
3. cell death creates joint cavity
4. surrounding mesenchymal cells differentiate into a joint capsule
73
discuss innervation of joints
innervated by same nerves that innervate the attached muscles and overlying skin
in addition to fibers carrying proprioceptive information, there are abundant pain fibers in the joint
74
arthrogryposis
congenital joint contractures
| neurological/muscle/joint defects
75
discuss the formation of limb muscles from myotomes (of somites)
begin in 7th week
condensation of mesenchyme near base of limb buds form (derivate of DL cells of somites)
initially segmented according to somite origin, but eventually form single muscle
limb patterning based on CT derived from LPM (parietal)
76
when do flexor and extensor compartments emerge
with elongation of limb buds
| additional splittings and fusions occur
77
Poland sequence
absence of pec minor
partial loss of pec major
nipple and areola are absent or displaced
breast development altered
can occur with digital defects on affected side
78
prune belly syndrome
partial or complete loss of abdominal muscles
organs visible through thin abdominal wall
urinary tract malformations may be present
79
what are muscular dystrophies
inherited muscle diseases that cause progressive muscular wasting and weakness
some caused by mutations in gene for dystrophin
80
what is dystrophin
cytoplasmic protein
forms protein complex linking contractile elements to cell membrane
maintains cell structure of myocytes and enables contraction
81
what happens to muscle cells lacking dystrophin
degenerate and die
replaced by fibrous tissue
remaining muscle cells hypertrophy
82
Duchenne MD
```
X-linked recessive, 1 in 4,000 male births
NO functional dystrophin made
early onset < 5 yo
progressive muscle weakness
lifespan ~20 years
```
83
Becker MD
```
X-linked recessive
dystrophin of altered MW is made
some dystrophin in muscles (milder presentation)
onset around puberty
lifespan ~40-50
```
84
motor innervation of developing musculature
due to vertebral level from which muscle cells originate
85
limb muscle innervation
innervated by primary ventral rami of spinal nerves from its spinal segment
divide to form dorsal and ventral branches to compartments
branches unite to form larger nerves
contact between nerves and muscle cells necessary for differentiation
86
sensory innervation of musculature
spinal nerves
reflects embryological origin and innervation of skin dermatomes (NOT somite dermatome)
dermatome pattern changes with growth and rotations of extremities; but retains segmental pattern
87
blood supply to the limbs
supplies by branches of intersegmental arteries from the aorta
primary axial artery and its branches form in limbs, vascular pattern progresses via angiogenesis to form vessels of upper and lower limbs
88
molecular regulation of proximal-distal limb development
outgrowth from body wall: FGF10 from LPM
formation of AER: BMPs in ventral ectoderm
restriction of AER to distal limb tip: SER2 from RADICAL FRINGE in dorsal limb ectoderm
establishment of AER: SER2 at border we ENGRAILED-1
89
what factors does AER express
FGF4 and 8
| maintain progress zone/undifferentiated zone of proliferating mesenchyme near AER
90
what induces patterning of 3 limb segments
depends on relative distance from signals
retinoic acid - stylopod
SHH - zeugopod
FGF stops - autopod
91
what is anterior to posterior limb development
thumb to pinky development
92
how is anterior to posterior limb development regulated
zone of polarizing activity (ZPA)- cluster of mesenchymal cells at posterior border of limb, near AER
93
what is the function of ZPA
produced retinoic acid which leads to expression of SHH
contributes to specification of posterior in AP axis
as limb grows, ZPA moves distal in proximity to posterior border of AER
94
what happens if anterior to posterior limb development is dysregulated
abnormal expression of SHH by ZPA misplaced to anterior border leads to duplication of ZPA and SHH
signaling
results in mirror duplication of posterior limb structures (little fingers)
95
function of HOX gene
gene expression in limbs that correspond to 3 limb segments
| regulates types and shapes of bones
96
molecular regulation of dorsal-ventral limb development
BMPs in ventral ectoderm induce EN1
WNT7 in dorsal ectoderm induce LMX1
EN1 repressed WNT7 (act antagonistically)
97
amelia
complete absence of upper and/or lower limbs
98
meromelia
partial absence of limbs
99
phucomelia
long bones absent; rudimentary hands/feet attached to trunk
100
micromelia
all segments of limb present, but short
101
effects of thalidomide on limb development
when taken by pregnant women, leads to defects
absence or gross deformities of long bones
intestinal and cardiac abnormalities as cell
4th and 5th weeks of development are most sensitive for teratogens
102
origin of teeth
arise from interactions between oral epithelium and neural crest derived mesenchyme
NOT bones
harder than bones due to dentine
103
structure of bones
composed of minerals but are mostly collagen
exterior lined by periosteum w/ osteoblasts
interior BM produces RBCs and WBCs
104
structure of teeth
composed of minerals
exterior is enamel (non regenerative)
interior dental pulp does not produce blood cells
105
when does tooth development occur
3 months
106
overview of tooth development
buds for permanent teeth form and lie on lingual aspect of milk teeth
buds remain dormant until age 6
buds grow and push against milk teeth
milk teeth lost
107
what happens as permanent teeth grow
root of overlying deciduous tooth is resorbed by osteoclasts
108
natal teeth
premature baby teeth present in newborns
| may or may not survive
109
hypodontia
6 or fewer permanent teeth missing
110
oligodontia
more than 6 permanent teeth missing
111
when should you have your first dental visit
by 1 year of age
