Int. J. Dev. Biol. In Press
doi: 10.1387/ijdb.200166jc
© UPV/EHU Press

Inhibition of WNT/ß catenin is necessary and sufficient to induce Scx expression in developing tendons of chicken limb

Valentina Garcia-Lee, Martha Elena Díaz-Hernandez and Jesús Chimal-Monroy*

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México

ABSTRACT The cell differentiation of the musculoskeletal system is highly coordinated during limb development. In the distal-most region of the limb, the WNT and FGF signaling released from the apical ectodermal ridge maintain the mesenchymal cells in the undifferentiated stage. Once the cells stop receiving WNT and FGF signaling, they respond to differentiation signals. Particularly during tendon development, the mesenchymal cells enter the cell differentiation program once Scleraxis (Scx) gene expression occurs. Among the signals that trigger the cell differentiation programs, TGFβ signaling has been closely involved in tendon differentiation. However, whether the Scx gene expression depends merely on TGFβ signaling or other signals is still not fully understood. In the present study, considering that WNT/β catenin is an inhibitory signal of cell differentiation, we speculated possible antagonistic or additive effects between canonical Wnt/β catenin and TGFβ/SMAD signaling pathways to control the Scx gene expression. According to our results, the blockade of WNT/β catenin promoted the Scx gene expression. In contrast, the inhibition of TGFβ/SMAD signaling did not maintain the Scx gene expression. Interestingly, the blockade of both WNT/β-catenin and TGFβ/SMAD signaling at the same time promoted the Scx gene expression. Thus, as our results suggest, the inhibition of WNT/β signaling is necessary and sufficient to induce Scx gene expression.

Keywords:

Scleraxis, tendon differentiation, limb development, TGFβ, Wnt signaling

*Corresponding author e-mail: jchimal@unam.mx