MSK Embryology Flashcards
Define gastrulation
Epilast ingression through the primitive streak to form a three layered structure - trilaminar disk - ecto, meso and endoderm
What is neurulation?
Ectodermal cells fold and regulated by transcription factors to form the nervous system
What is the origin of most musculoskeletal features in the head and neck?
Ectomesenchyme
Originating from neural crest cells
What is the different basic origin of the skull?
The frontal and temporal part of the skeleton - neural crest-derived structures (EMT is ventral and lateral)
Occipital and parietal - mesdermal tissues
What are the two different ways bone can form in the skull?
Intramembranous ossification
Endochondral ossification
What is endochondral ossification?
What parts of the skull does it form?
Cartilage that ossifies
Contributes to the viscerocranium and the chondrocranium.
(sphenoids, part of occipital, otic capsules and nasal capsules)
Bones of facial expression (maxilla, mandible, vomer, zygomatic)
What are the bones of the viscerocranium?
Lacrimal
Nasal
Zygomatic
Ethmoid
Vomer
Inf nasal concha
Maxilla
Mandible
What are the implications of the cranial vault forming by intramembranous ossification?
Limited ability to increase further in size - bones tend to reach a fixed ossification and size early in life
Reduces room for bone growth
Means the majority of growth occurs as the cranial sutures and fontanelles -> these contain mesenchymal precursors that have not yet undergone ossification.
One of the reasons for large variability in head and skull shape
What is craniosynostosis?
Abnormal head shape
Due to premature fusion of head sutures.
As the brain continues to grow witll push out in other directions causing abnormal patterns of head growth in alternative suture weakness areas.
What signalling molcule mainly regulates the formation of bone?
FBG 2>3>1 for bone cells
FGF signalling drives differentiation of mesenchyme into osteoblasts, high levels of functional FGF molecules and receptors are required for osteogenic differentiation.
What mutation is considered to cause craniosynostosis?
Mutations in the FGF signalling molecules or receptors.
What are some examples of craniosynostosis?
Scaphomegaly
Brachycephaly
Trigoncephaly
Plagocephaly
What is scaphomegaly?
Premature fusion of the sagittal suture
results in forward growth of the skull
What is brachycephaly?
Premature fusion of the coronal suture
Results in abnormal lateral growth of the skull
(BUtch on the sides)
What is trigoncephaly?
Premature fusion of the frontal suture
Triangle shaped skull - growth out at the back of the skull (occipital area)
What is plagocephaly?
Fusion of coronal suture on one side
Point - curves to opposite side at the front
What cell populations contribute to the development of the axial MSK?
Paraaxial mesoderm
What structures does the intermediate mesoderm differentiate into?
Kidney
Gonads
What structures does the cordamesoderm differentiate into?
Notochord
Intervertebral disc
What does the paraxial mesoderm develop into?
Somites (own slide)
Paraxial = head
What are the different lineages of differentiation for somites?
Sclerotome
Dermomyotome
What does the sclerotome differentiate into?
Vertebrae and ribs
Endotome = endothelial cells, dorsal aorta
Arthortome = vertebral joints
Syndetome = tendon
What does the dermomyotome differentiate into?
Myotome = skeletal muscle
Dermatome = dermis, skeletal muscle
Mainly on the back
What embryological structure forms the majority of the axial MSK system?
Somites
Describe the basic anatomy that underpins the development of somites.
Embryo grows from the back = growth zone
Cells in the tail bud/growth zone gastrulate - undergo EMT to migrate into the presomitic mesoderm then undergo a MET to become a somite
What model describes the process of somitogenesis?
Clock and wave front signalling
What is the wave front process of somitogenesis?
Influence of FGF8 and retinoic acid
From the back - conc gradient of FGF8
From the front - conc gradient of retinoic acid (Raldh2)
At mid point where FGF8 and Raldh2 are both low the Mesp gene is expressed
This is a transcription factor that drives the mesenchymal to epithelial transition to form somites
The point of gradient boundary is known as the wavefront/determination front.
The wavefront moces as more somites are produced hence the location of max retinoic acid conc changes
What is the role of Notch signalling in somitogenesis?
Forms the wave of the model
Notch signalling oscillates -> is cell to cell signalling -> gaps in signalling correspond to gaps between somites
Prevents formation of just one very long somite
What is the role of Hox gene signalling in somitogenesis?
Controls the positional identity of each somite
Uses a cranial caudal axis - relates to knowing a thoracic v a lumbar vertebrae.
What is spinal dystosis?
A group of conditions characterised by abnormal development of bones in the spine and ribs - vertebrae are misshapen and abnormally fused - short torsa, restricted chest expansion and breathing difficulties.
What is the embryological origin of the appendicular skeleton?
The lateral plate mesoderm
What is the importance of positional identity in appendicular MSK development?
Regulated by hox genes - various combinations and concentrations gives identity
Why we have legs on the bottom and arms on the top
What process controls the outgrowth of limbs? (appendicular skeleton)
Retinoic acid and FGF signalling gradient
RA proximally and FGF distally
The concentration balance regulates Hox gene expressions -> gives positional identity of the stylopod, zuegopod and the autopod.
What are the key timing of bone development in embryology?
Patterning established
Mesenchyme -> cartilage (begins around week 6)
Primary ossification centres develop grossly at week 10 until late adolescence/early adulthood
Continues through secondary ossification centres into adulthood - responsible for most bone growth between birth to adulthood.
After birth where in the bone does most growth occur?
The growth plate - chondrocytes proliferate and eventually ossify.
What signalling process regulates primary/secondary ossification centres?
Sox9 - specifies cartilage progenitors
Runx2 - drives osteogenesis
Both these transcription factors are reciprocally regulated.
Ihh - drives chondrocyte proliferation
FGF - inhibits proliferation nad differentiation postnatally
What is the underlying disease process of achondroplasia?
Long bone dwarfism
Activating mutation of FGFR3 - results in increased inhibition of proliferation and differentiation in osteogenesis postnatally.
This effects endochondral ossification
What is the embryological link to osteosarcoma?
Affects mianly long bones
Originates from mesenchymal pluripotent stem cells
Early onset as these centres of ossification are most active in childhood/teenage years.
