On the development of the patella.
The current view of skeletal patterning fails to explain the formation of sesamoid bones. These small bones, which facilitate musculoskeletal function, are exceptionally embedded within tendons. Although their structural design has long puzzled researchers, only a limited model for sesamoid bone development has emerged. To date, sesamoids are thought to develop inside tendons in response to mechanical signals from the attaching muscles. However, this widely accepted model has lacked substantiation. Here, we show that, contrary to the current view, in the mouse embryo the patella initially develops as a bony process at the anteriodistal surface of the femur. Later, the patella is separated from the femur by a joint formation process that is regulated by mechanical load. Concurrently, the patella becomes superficially embedded within the quadriceps tendon. At the cellular level, we show that, similar to bone eminences, the patella is formed secondarily by a distinct pool of Sox9- and Scx-positive progenitor cells. Finally, we show that TGFβ signaling is necessary for the specification of patella progenitors, whereas the BMP4 pathway is required for their differentiation. These findings establish an alternative model for patella development and provide the mechanical and molecular mechanisms that underlie this process. More broadly, our finding that activation of a joint formation program can be used to switch between the formation of bony processes and of new auxiliary bones provides a new perspective on plasticity during skeletal patterning and evolution.
Weizmann Institute of Science, Department of Molecular Genetics, PO Box 26, Rehovot 76100, Israel.
Shai
S
Eyal
Weizmann Institute of Science, Department of Molecular Genetics, PO Box 26, Rehovot 76100, Israel.
Einat
E
Blitz
Weizmann Institute of Science, Department of Molecular Genetics, PO Box 26, Rehovot 76100, Israel.
Yulia
Y
Shwartz
Gifu University, Department of Orthopedics, Gifu City 501-1194, Japan.
Haruhiko
H
Akiyama
Research Division, Shriners Hospital for Children, Portland, OR 97201, USA.
Ronen
R
Schweitzer
Weizmann Institute of Science, Department of Molecular Genetics, PO Box 26, Rehovot 76100, Israel eli.zelzer@weizmann.ac.il.
Elazar
E
Zelzer
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D017403:In Situ Hybridization; D007596:Joints / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D010329:Patella / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012716:Sesamoid Bones / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D055415:Bone Morphogenetic Protein 4
BMP4; Joint formation; Mechanoregulation; Morphogenesis; Mouse; Patella; Progenitor cell; Scleraxis; Sesamoid bone; Skeletogenesis; Sox9; TGFβ