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Publication : CXXC Finger Protein 1 drives BMP signaling and progenitor cell differentiation during limb development.

First Author  Pignatti E Year  2025
Journal  Dev Biol Volume  528
Pages  204-215 PubMed ID  40915528
Mgi Jnum  J:372665 Mgi Id  MGI:8250005
Doi  10.1016/j.ydbio.2025.09.004 Citation  Pignatti E, et al. (2025) CXXC Finger Protein 1 drives BMP signaling and progenitor cell differentiation during limb development. Dev Biol 528:204-215
abstractText  The mechanisms mediating endochondral bone formation remain incompletely understood. Here, we show that CXXC Finger Protein 1 (CFP1) is required for the onset of chondrogenesis during forelimb development. CFP1-deficient mesenchymal progenitor cells (LMPs) retain an immature molecular signature with elevated FGF and SHH signaling and repressed BMP signaling, in part, due to (1) reduced expression of type I BMP receptors, (2) reduced Smad1 protein levels and (3) an altered extracellular niche. Moreover, the addition of exogenous BMP ligand or antagonism of heparan sulfate restores LMP differentiation toward a chondrogenic fate and enhances BMP signaling, suggesting a defect in BMP ligand bioavailability mediates the CFP1-deficient LMP phenotype. Together, these findings define CFP1 as a gatekeeper between the undifferentiated and differentiated state of LMPs during endochondral bone formation and as a physiological regulator of BMP signaling. CLASSIFICATION: Biological Sciences.
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