Mesodermal Structures Quiz

Mesodermal Structures

• The title of the document/lecture is Mesodermal Structures, authored by Lerrie Ann Ipulan-Colet, Gilbert and Barresi, 11th Edition.

Somitogenesis: Directionality and Size

• Questions about somitogenesis:
  • Is there directionality in somite creation?
  • Are somites of the same size?
  • Which somite is older, SIV or SI?

Boundary Formation

• Questions pertaining to boundary formation:
  • What events are needed for A/P elongation of somites?
  • Which signals inhibit and induce somitogenesis?
  • Which signal is responsible for somite epithelialization?
  • What morphogenetic/cellular event is necessary for epithelium formation?

Analogies in Somitogenesis

• Analogies in somitogenesis:
  • Morphological analogies- pan deasal/bread making, candy, chorizo/longanisa, plant nodes/internodes
  • Molecular analogies- toxic jowa, sunscreen/sunburn.

Partitions and Lineages of the Mesoderm

• Parts and lineages:
  • Neural tube
  • Intermediate mesoderm
  • Chordamesoderm
  • Paraxial mesoderm
  • Lateral plate mesoderm
  • Notochord
  • Somite
  • Kidney
  • Gonads
  • Head
  • Intervertebral disc
  • Sclerotome
  • Myotome
  • Dermatome
  • Syndetome

Somitogenesis: Formation

• Points of discussion:
  • Epithelialization- expression of fibronectin, cadherins. May be due to transcription factor (Paraxis)
  • Specification- axial specification happens early (e.g., only certain somites form ribs).
  • Epithelial Mesenchymal Transition (EMT)
  • Differentiation within somites
  • Watch Barressi video

Somitogenesis: Determination

• Elements in somitogenesis determination:
  • BMP4
  • NT3, Wntl, Pax3, 7
  • Wnt
  • Wnt3a
  • Myf5, Pax3
  • MyoD
  • Pax1
  • BMP4, FGF5
  • Shh
  • Noggin
  • Epidermis
  • Dermatome
  • Abaxial (body wall and limb) muscles
  • Lateral plate mesoderm
  • Sclerotome
  • Dermomyotome
  • Neural tube
  • Floor plate
  • Notochord
  • Shh

EMT in the Somite

• Elements in EMT in somite:
  • Embryo diagrams (2 days, 3 days, 4 days and late 4 days)
  • Epidermis
  • Neural tube
  • Sclerotome progenitors
  • Floorplate
  • Notochord
  • Dermomyotome
  • Primaxial dermomyotome lip
  • Primaxial myotome
  • Sclerotome
  • Dermatome region
  • Paxl – migrating sclerotome
  • Abaxial myotome
  • Abaxial dermomyotome lip
  • Central myotome region

Epimere/Somites

• Epimere/somite divisions:
  • Sclerotome development
    • Vertebrae development
    • Bone development
  • Dermomyotome development
    • Myotome
    • Dermatome
    • Migrating myoblast

Somite Differentiation

• Questions about Somite Differentiation:
  • What is the collective term for A?
  • What is the collective term for B?
  • What structures do D contribute?
  • What do cells in C contribute to?
  • What do cells in E contribute to?

Endochondral Bone Formation

• Information about Endochondral Bone Formation:
  • Involves blood vessel invasion of the cartilage model
  • Hypertrophic chondrocytes die via apoptosis
  • Osteoblasts deposit bone matrix in periphery
  • Mesenchyme (in sclerotome, limbs)
    • Induced to secrete Pax I and Scleraxis
    • Activates cartilage-specific genes
    • Chondrocytes proliferate rapidly to form the model
    • Chondrocytes secrete cartilage-specific ECM
    • Committed mesenchyme cells
  • Compact nodules
  • Chondrocytes
  • N-cadherin
  • N-CAM
  • Cells become hypertrophic chondrocytes
  • Matrix alters by adding collagen X and fibronectin
  • Mineralized calcium are easily deposited
  • Cartilage
  • Hypertrophic chondrocytes
  • Osteoblasts
  • Blood vessels

Endochondral Bone Development

• Points about Endochondral Bone Development:
  • Sox Trio - master regulator of early chondrogenesis
    • Commitment of mesenchymal cells to cartilage (Sox 9)
    • Secretion of critical collagen (Sox 9)
    • Sox5 and 6 deficient mice have chondroplasia
  • BMP
    • Mesenchymal condensation
    • Pro-proliferation and anti-differentiation
  • FGFr3
    • Accelerate chondrocyte proliferation and differentiation
    • Constitutive active mutations lead to skeletal dysplasia (ex, short limbs and dwarfism)
  • PTHrP
    • Gatekeeper of zone of hypertrophic chondrocytes
    • Control switch from proliferative immature chondrocyte to post-proliferative hypertrophic chondrocyte

Runx's New Role

• Runx's New Role
  • Runx2 essential for specifying osteoblast lineage
  • Directly regulates another transcription factor (Osterix)
  • Regulates Coll0al and matrix metalloproteinase-13 (Mmp13) expression in chondrocytes
  • Osx essential for preosteoblast differentiation
  • Osx transactivates Collal
    • Encodes collagen I, a marker of differentiated osteoblasts
  • Hypertrophic chondrocytes can become osteoblasts and osteocytes

Growth Plate and Hormonal Influence

• Growth Plate and Hormonal Influence:
  • Influenced by growth hormone and IGF
  • Puberty growth spurt due to sex hormones
  • Growth plate closure eventually
  • Absence of sex hormone (estrogen)
    • Leads to osteoporosis in menopausal women

Development of Dermal Bones

• Dermal Bone Development:
  • Derived from intramembranous ossification
  • Skull, jaws, gill covers, fin spines, rays, and shell in humans
  • Human skull from both neural crest cells (NCC) and mesoderm
  • BMP2, 4, and 7 induce neural crest cells
  • Expression of cbfa genes
    • Leads to expression of bone-specific ECM proteins

Development of the Skull

• Development of the Skull:
  • FEZ regulates growth and frontonasal patterning
  • D-V patterning (Chick model)
    • FEZ/frontonasal ectodermal zone
    • Midfacial ectoderm coordinates frontonasal and plate development
    • Fgf8 and Shh boundary
  • Osteo progenitors migrate and add to leading edges of developing bones
  • Signaling impacts suture maintenance for further growth
    • Bmp - bone formation
    • Jag1 - osteogenic font
    • Twist – mifration

What is Craniosynostosis?

• Craniosynostosis:
  • Sagittal suture (affected suture) is fused prematurely

Other Structures from Sclerotome

• Other Structures from Sclerotome:
  • Tendons- scleraxis-expressing part of the scleretome
  • Dorsal aorta- posterior sclerotome origin of ECs and vSMCs
  • Other arteries- lateral plate mesoderm
  • EC differentiation induced by Notch sign in Ephrin B2-dependent manner

Myogenesis of Skeletal Muscle Fiber

• Myogenesis of Skeletal Muscle Fiber:
  • Formation of non-specific muscle masses
    • Break up into discrete units (primordia) of individual muscles
  • Differentiation of myotubes from myoblasts
  • Innervation
    • Motor innervation
    • Sensory innervation

Factors Regulating Muscle Development

• Factors regulating muscle development:
  • Insulin-like growth factor-1 and -2
    • Stimulates proliferation
    • Stimulates differentiation
  • Fibroblast Growth Factor
    • Stimulates proliferation
    • Inhibits differentiation
  • Transforming growth factor beta
    • Suppresses proliferation
    • Suppresses differentiation
  • Myostatin
    • Negative regulator

Model of Muscle Cell Development

• Model of Muscle Cell Development:
  • Specification and formation of myoblast
  • Myoblasts --> proliferation
  • Myogenin (active) --> differentiation
  • Myotubes
  • p21
  • p57
  • Cyclin Dependent Kinases
  • Growth Factors (ex, IGF1)

Categorizing Factors That Affect Myogenesis

• Categorizing Factors:
  • Column A (pro-myogenesis)
    • Pro-proliferation
    • Pro-differentiation
    • Pro-increase in muscle size
  • Column B (anti-myogenesis)
    • Anti-proliferation
    • Anti-differentiation
    • Anti-increase in muscle size

Defect in Bone/Muscle Formation

• Defect Information:
  • Mechanisms of defects (2-3 sentences)
  • Biological effect (2-3 sentences)
  • How to ameliorate the defect (2-3 sentences)
  • Reference list