Most craniofacial membrane bones are derived from neural crest (NC) ce
lls. Interaction between NC cells and epithelium, and cellular condens
ation, are two major events that lead NC cells to become osteoblasts t
hat deposit membrane bone. Unlike endochondral bone, membrane bone for
mation is not preceded by cartilage formation in normal development. H
owever, chondrogenic potential in membrane bone is evidenced by severa
l cartilage-associated phenomena in vivo. Furthermore, in vitro, perio
steal cells of some membrane bones express cartilage phenotype gene pr
oducts and even differentiate into chondrocytes. Hence, membrane bone
pe riosteal cells can undergo chondrogenic differentiation. The precur
sor of chondrogenic cells in membrane bone is not clear: chondrocytes
were proposed to arise from unipotential chondroprogenitor cells, bi-
or multipotential progenitor cells, or differentiated osteogenic cells
. There is experimental support for each, but studies on clonal and ce
ll cultures provided more support for a common precursor of both chond
ro-and osteogenic cells. Moreover, in periostea, chondrogenesis probab
ly arises from a differentiated cell type. Membrane bone formation in
periostea may include a transient cell stage that is able to undergo b
oth osteo-and chondrogenesis. Osteogenesis would be the normal pathway
, but chondrogenesis can be evoked in certain microenvironments. It is
not known whether microenvironmental factors trigger chondrogenesis t
hrough a universal molecular mechanism, nor is the molecule that trigg
ers chondrogenesis known. Expression of neural cell adhesion molecule
(NCAM) is down-regulated during commitment of periostal cells for seco
ndary chondrogenesis, suggesting a possible regulatory role for NCAM i
n the alternative differentiation pathways of periosteal cells.