Study Questions – Lecture 16
1. What are the three osteogenic embryonic primordia?
-somites that lead to axial skeleton
-lateral plate mesoderm that forms limb skeleton
-cranial neural crest that forms craniofacial bones and cartilage
2. What are the two modes of osteogenesis and how are they fundamentally different
from one another?
Intramembranous ossification involves the direct conversion of mesenchymal tissue into
Endochondral ossification involves the differentiation of mesenchymal cells into cartilage
which is later replaced by bone.
3. Outline five general steps of endochondral ossification.
1) commitment of mesenchymal cells to becoming cartilage producing cells (Shh induces
sclerotome cells to express Pax1 transcription factor)
2) committed mesenchyme cells condense into compact nodules and differentiate into
chondrocytes = cartilage cells (BMP signalling required – induces expression of N-
cadherin, N-CAN, Sox9; Sox9 turns on other genes including collagen2)
3) chondrocyte proliferation – a cartilage model of the bone is made as chondrocytes
secrete a cartilage specific extracellular matrix
4) chondrocytes stop dividing and increase volume dramatically to become hypertrophic
chrondrocytes (requires Runx2 = Cbfa1)
5) blood vessels induced by VEGF invade the cartilage
4. Which of the cell types associated with ossification are derived from the sclerotome?
Which are not derived from the sclerotome?
Sclerotome leads to axial skeleton, including cell types such as chondrocytes and
osteocytes. Blood vessel cells are not from sclerotome.
5. If it were possible to do a fate map analysis of the sclerotome, would chondroycytes
and osteocytes map to different areas? What transcription factors are activated to
separate these lineages?
Chondrocytes and osteocytes would map to the same area as they are derived from the
same population of sclerotome cells. Their differentiation is influenced by paracrine
factors which lead to differential expression of transcription factors. Sox9 is associated
with chondrocyte fate, while Runx2 and Osterix lead to osteocyte fate.
6. What structures are derived from sclerotome? Outline the spatial and regulatory
relationships by which the sclerotome is specified. (include Shh, FGF, Pea3/ERM, scleraxis, Sox9, Sox5/Sox6 – indicate the source of Shh, the source of FGF, and the
Sclerotome will form the vertebrae as well as the syn