Figure 6.

Hes1-marked early mesenchymal cells surrounding the condensation behave as skeletal progenitors in endochondral bone development. Early perichondrial population of skeletal progenitor cells in endochondral bone development. Undifferentiated mesenchymal cells surrounding condensation or outer perichondrial cells outside the cartilage template provide an important source during fetal endochondral bone development. During the condensation stage, Hes1⁺ undifferentiated mesenchymal cells take two distinct routes to participate in endochondral bone development. First, these cells translocate into the cartilage template and directly differentiate into Sox9⁺ chondrocytes and then contribute to bone formation (chondrocyte-dependent pathway). Second, these cells contribute to the outer layer of the perichondrium and become Hes1+ perichondrial cells. These Hes1+ perichondrial cells translocate into the nascent marrow space and directly differentiate into marrow mesenchymal cells by bypassing a Sox9+ state (chondrocyte-independent pathway). These perichondrial skeletal progenitor cells keep providing osteoblasts and bone marrow stromal cells even during the postnatal stage. As a result, postnatal bone marrow is characterized by transitional mosaicism composed of both chondrocyte-derived and perichondrium-derived stromal cells.