What is it about?
Synovial joints arise from a progenitor cell population termed the joint interzone. Prior work has indicated that the transcription factor Creb5 induces the expression of signaling molecules that promote the formation of the joint interzone. We document that Creb5 auto-regulates its own expression in the joint interzone by binding to its own two promoters; and directly binds to enhancer elements in both the Gdf5 and Sfrp2 loci, which all require Creb5 binding sites to drive transgene expression in the developing joint interzone.
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Why is it important?
Our findings indicate that Creb5 initiates a regulatory network that both promotes the formation of synovial joints, and subsequently activates distinct transcriptional targets in different regions of the joint-interzone; thus regionalizing gene expression in the developing joint.
Perspectives
Pictured is the expression of two transcription factors: Creb5 (orange), expressed in articular cartilage and synovial lining cells; and Sox9 (green), expressed in the cartilage templates of the developing bones and meniscus in the mouse knee joint. Zhang et al. found that Creb5 both autoregulates its own expression and directs the expression of a regulatory program that induces synovial joint formation. Image Credit: Cheng-Hai Zhang and Andrew B. Lassar
Andrew Lassar
Harvard University
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This page is a summary of: Creb5 controls its own expression and directly induces the joint interzone regulatory program, Proceedings of the National Academy of Sciences, June 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2501830122.
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