Lecture 4 (musculoskeletal development) Flashcards
Which germ layer gives rise to the most body parts?
mesoderm
Which type of mesoderm is the greatest contributor to body parts?
paraxial (somitic) mesoderm
What gives rise to segmented epithelial somites?
paraxial mesoderm
What are the 4 types of somites? What does each give rise to?
- dermatome -> dermis of back
- myotome -> skeletal muscle
- syndetome -> tendons
- sclerotome -> vertebrae, ribs, cartilage
What day does the 1st somite appear?
around day 20
How do somites appear?
ordered sequence cranial to caudal along neural tube
A new somite arises once every:
90 minutes
The neural tube begins to close at which somite level?
4th
How many pairs of somites exist?
44
Somites differentiate into what two types?
sclerotome and demomyotome
Upper and lower halves of __________ form vertebrae during the _____ wk.
sclerotome, 4th
Dermomyotome divides in:
dermotome and myotome
What two components does myotome become?
- epaxial division (dorsal side)
- hypaxial division (ventral side)
What are the three muscle types? What do they form from?
- skeletal -> paraxial
- smooth -> splanchic (visceral) layer of lateral plate mesoderm
- cardiac -> splanchic (visceral) layer of lateral plate mesoderm
The epaxial division of the myotomes become: ________. What innervates these?
muscles of back and neck
dorsal primary ramus
The hypaxial division of the myotomes become: ________. What innervates these?
trunk, back, and limb muscle
ventral primary ramus
What role does BMP4 play in somite differentiation?
produced by ectodermal region and activates WNT from neural tube
In somite differentiation, the notochord releases ___________. This leads to:
SHH and Noggin
formation of sclerotome and expression of PAX1 (vertebral formation)
WNT and SHH acting on somites produce lead to expression of ________ and formation of:
PAX3
dermatome
WNT and SHH act on the epaxial region of myotome to express:
MYF5
WNT and BMP4 act on the hypaxial region of myotome to express:
MYOD
MYF5 and MYOD are:
transcription factors that activate pathways for muscle development
Hox genes are for:
patterning of axes and the vertebrae
Vertebrae are formed by:
fusion of the upper and lower halves of two successive sclerotomes
What are the two types of bone formation?
endochondrial ossification
intramembranous ossification
Outline steps to endochondrial ossification:
- mesenchymal cells in sclerotomal core condense and commit to cartilage lineage
- chondrocytes condense to form template (6th wk)
- chondrocytes in center express VEGF and undergo apoptosis
- extracellular matrix of apoptotic cells mineralize
- blood vessels invade space, osteoblasts differentiation
What happens in premature bones once osteoblasts differentiate?
- osteoblasts secrete mineral matrix on template
- continues
- blood vessel enters @ secondary sites and start other ossification centers
- epiphyseal plate continues to produce cartilage
Endochondrial ossification allows for what w/ long bones? How long does it continue?
- allows for long bones to lengthen
- continues until 20 years old roughly
What occurs in intramembranous ossification? Does it require a cartilage template?
mesenchymal cells directly differentiate into osteoprogenitor cells
no template
What two structures are formed through intramembranous oss?
- neurocranium
2. viscerocranium (face)
The neurocranium consists of what two things?
- membranous neurocranium (flat bones)
- cartilaginous neurocranium (base of skull)
The viscerocranium originates from what cell type?
neural crest cells
the membranous neurocranium is derived from:
neural crest cells and paraxial mesoderm
The fissures that separate the flat bones of the skull are called:
sutures
what are fontanels?
areas of the skull where >2 sutures meet
When do sutures usually close?
during 1st or 2nd year of life
What is craniosynostosis? What’s a major cause?
premature closure of at least one cranial suture
mutations in FGFRs
Scaphocephaly is a result of:
premature closure of sagittal suture
Brachycephaly is a result of:
premature closure of coronal suture
Plagiocephaly is a result of:
premature closure of unilateral coronal and lamboid sutures
Cloverleaf skull is a result of:
premature closure of most cranial sutures
When do limb buds become visible?
by wk 5
Limb development begins with the formation of the:
apical ectoderm ridge (AER)
What initiates limb outgrowth?
FGF10 secreted by lateral plate mesoderm
What molecules lead to AER formation?
induced by bMP and restricted to distal portion of radical fringe -> induces SER-2 expression in cells destined to b AER
What molecules does the AER express to maintain progress/undifferentiated zone?
FGF4 and FGF8
What molecule is antagonistic to FGF and produced by differentiated cells?
retinoic acid
In limb development, RA is expressed in which region?
stylopod
In limb development, Shh is expressed in which region?
Zuegopod
The autopod is differentiated thanks to this molecule:
FGF
the AER creates separate digit ridge by day:
48
digits begin to separate by day _____ thanks to:
51, cell death
digit separation is complete by day ______.
56
What region of the limb is responsible for anterior-posterior patterning?
ZPA
What molecule does the ZPA produce? Do higher levels lead to anterior or posterior digits?
Shh
posterior
When does limb rotation occur?
8th week
The upper limbs rotate:
laterally
Lower limbs rotate:
medially
TBX5 leads to development of the _____limb.
fore
TBX4 leads to development of the ____limb.
hind
