Figure 7

Proposed model for the consecutive roles of BMP and RA to induce the stepwise progression of chordoblasts from solely matrix-producing towards solely matrix-mineralizing cells. I. Chordoblast contribution to chordacentra formation starts with collagen II-based matrix (notochord sheath) production. II. Next, cells progress into a matrix-secreting and -mineralizing transitory stage induced by BMP, with an induction of entpd5a expression, required for matrix mineralization (thick blue arrow) and with some minor positive effect on col2a1a expression (thin blue arrow). III. Lastly, RA signaling enhances and maintains entpd5a transcription (thick red arrow), thereby reaching Entpd5a levels that allow for sustained bio-mineralization of the notochord sheath. At the same time RA represses col2a1a transcription to attenuate matrix secretion. Chordoblasts can only enter step III after they have experienced BMP signaling beforehand (black arrow with blue lining).