RT Journal Article
SR Electronic
T1 Development of migrating entheses involves replacement of progenitor populations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 210799
DO 10.1101/210799
A1 Neta Felsenthal
A1 Sarah Rubin
A1 Tomer Stern
A1 Sharon Krief
A1 Deepanwita Pal
A1 Brian A. Pryce
A1 Ronen Schweitzer
A1 Elazar Zelzer
YR 2017
UL http://biorxiv.org/content/early/2017/10/29/210799.abstract
AB Attachment sites of tendons to bones, called entheses, are essential for proper musculoskeletal function. They are formed embryonically by Sox9+ progenitors and undergo a developmental process that continues into the postnatal period and involves Gli1 lineage cells. During bone elongation, some entheses maintain their relative positions by actively migrating along the bone shaft, while others, located at the bone’s extremities, remain stationary. Despite their importance, we lack information on the developmental transition from embryonic to mature enthesis and on the relation between Sox9+ progenitors and Gli1 lineage cells. Here, by performing a series of lineage tracing experiments, we identify the onset of Gli1 lineage contribution to different entheses during embryogenesis. We show that Gli1 expression is regulated by SHH signaling during embryonic development, whereas postnatally it is maintained by IHH signaling. Interestingly, we found that unlike in stationary entheses, where Sox9+ cells differentiate into the Gli1 lineage, in migrating entheses the Sox9 lineage is replaced by Gli1 lineage and do not contribute to the mature enthesis. Moreover, we show that these Gli1+ progenitors are pre-specified embryonically to form the different cellular domains of the mature enthesis.Overall, these findings demonstrate a developmental strategy whereby one progenitor population establishes a simple, embryonic tissue, whereas another population is responsible for its maturation into a complex structure during its migration. Moreover, they suggest that different cell populations may be considered for cell-based therapy of enthesis injuries.