Paraxial Mesoderm

Paraxial Mesoderm

adjacent to notochord, produces bone, muscles, and cartilage of the back, muscles of the limbs, and forms somites

Synthesizes noggin early in development

Somites

blocks of tissue present on either side of the neural tube, as a temporary stage in development. Give rise to vertebrae and ribs as well as other tissues

Somite formation

Paraxial mesoderm starts as bands of mesenchyme on either side of the neural tube, cells undergo mesenchymal-epithelial transition. Somites are formed starting at the anterior and moving posteriorly

Tissues produced by somites

Sclerotome ventral part of somite to form cartilage and bone of vertebrae and part of ribs, cells on side of somites will form muscle, cells of the upper side of the somite form dermis

Signaling of sonic hedgehog

Produced by the notochord to induce formation of the sclerotome

Wnt proteins

Produced by epidermis and dorsal portion of neural tube induce formation (with low levels of sonic hedgehog) of future muscle tissue

Formation of bone

Scherotome section of somites contributes to bone formation.

Endochondrial ossification

• Mesenchyme cells condense and clump together to differentiate and become chondrocytes.

  • N-cadherin required for start of condensation.

• Chondrocytes divide and establish shape of future bone. Secrete large amounts of extracellular matrix

• Swell up and termed hyptertrophic chondrytes

  • secrete vesicles which initiate mineralization of the cartilage by depositing calcium phosphate

  • secrete the signaling molecule VEGF-A

    • induces formation of blood vessels or formation of new blood vessel branches

  • secrete Indian hedgehog which promotes differentiation of osteoblasts

• Chondrocytes undergo programmed cell death and cavities are future bone marrow

• Osteoblasts secrete a matrix that binds calcium phosphate, matrix becomes calcified, eventually cartilage is replaced by bone

Bone growth

Regions of near ends of bones remain cartilaginous (epiphyseal growth plates) where chondrocytes keep proliferating.

At puberty, high levels of estrogen or testosterone signal the proliferating chondrocytes to differentiate, growing ends are replaced by bone, no more growth

Bone remodeling

• Bone removal allows bone marrow cavity to grow as bone does.

• Done by osteoclasts to break down bone matrix by exporting hydrogen ions and allows remodeling of bones to respond to external pressure

Too many osteoclasts

Can lead to fragile bones → osteoporosis

Fgf4 gene

Extra Fgf4 causes chondroblasts to stop dividing and differentiate early

ex. Dachshunds

Achondroplasia

Mutation in the gene for FGF receptor 3. The receptor is active when not bound to ligand. Extra FGF singaling causes chondroblasts to stop dividing and differentiate early.

Stress force on skeeltal tissue affects bone growth

In chick, some bones don’t form if movement of embryo is blocked.

Ex. fibular crest, bone in hind limb

BMPs and PhrP

• Maintain chondrocyte proliferation

• BMPs induce Sox9 and N-cadherin expression

Indian Hedgehog

activates PhrP and increases BMP levels

N-cadherin signaling

Involved in starting condensation of chondrocytes, stick together to condense and form dense bones

Stress force on skeletal tissues

Mechanical stress activates Indian hedgehog

Ex. force on mandibular cartilage from chewing affects monkey jaw size

Therapeutic application of parathyroid hormone or BMPs

releasing parathyroid hormone or BMPs into area of fracture over a long period of time should help with bone regrowth.

ex. collagen gel with gene for parathyroid hormone in bacterial plasmid

Therapeutic application - muscle stem cells were genetically modified so that they would produce signaling proteins

Cells producing BMP4 and ones producing VEGF were generated, combination of BMP4 and VEGF-A worked better than BMP4 alone in wounds in mouse skulls