New release: Temporally regulated FGFR2–retinoic acid signaling mediates dura mater–suture mesenchyme interactions to prevent craniosynostosis in mice
August 4th, 2026A new RNA-Seq dataset from the University of Southern California is now available in FaceBase!
Contributors: Lu Gao, Peng Chen, Jifan Feng, Tingwei Guo, Mingyi Zhang, Thach-Vu Ho, Jian-Fu Chen, Yang Chai (University of Southern California)
Description:
Congenital anomalies often arise during critical developmental time windows, yet the underlying mechanisms remain unclear. Here, we identify a time-specific FGFR2-retinoic acid signaling axis regulating postnatal coronal suture development through dura mater-suture mesenchyme interactions. FGFR2 signaling gradually declines after birth, leading to reduced retinoic acid signaling by moderating the expression of Aldh1a3 in the dura mater and suture mesenchyme alongside that of Rbp1 in the dura mater, thereby preserving GLI1+ progenitors and restraining osteogenesis to maintain suture patency. Importantly, FGFR2 overactivation in Fgfr2IIIc mutant mice within an early time window, disrupts this physiological FGFR2-retinoic acid signaling decline by upregulating Rbp1 and Aldh1a3 through enhanced P38 signaling. This leads to increased retinoic acid synthesis, premature osteogenic differentiation of GLI1+ progenitors, and coronal suture craniosynostosis.
Significantly, genetic restoration of retinoic acid signaling rescues craniosynostosis in Fgfr2IIIc mutant mice, confirming retinoic acid signaling as a key downstream effector of FGFR2 signaling. Notably, restoration of suture patency alone rescues neurocognitive dysfunctions in Fgfr2IIIc mutant mice despite Fgfr2 mutation in the brain, demonstrating that the neurocognitive impairments primarily arise from cranial structural constraints and elevated intracranial pressure rather than intrinsic neural defects. This critical postnatal time window in mice parallels the timing of FGFR2-related craniosynostosis onset in humans, underscoring the importance of this study in advancing our understanding of the molecular and cellular mechanisms in craniosynostosis. Our findings define a temporally regulated FGFR2-P38-retinoic acid signaling axis and highlight retinoic acid signaling as a promising therapeutic target in FGFR2 overactivation-related craniosynostosis.
FaceBase Dataset:
Lu Gao, Peng Chen, Jifan Feng, Tingwei Guo, Mingyi Zhang, Thach-Vu Ho, Jian-Fu Chen, Yang Chai. RNA-Seq elucidates the FGFR2-RA pathway in dura-suture interaction during Craniosynostosis. FaceBase Consortium https://doi.org/10.25550/8B-9CNW (2026).
Publication:
Gao, L., Chen, P., Feng, J., Guo, T., Zhang, M., Ho, T.-V., Chen, J.-F., & Chai, Y. Temporally regulated FGFR2–retinoic acid signaling mediates dura mater–suture mesenchyme interactions to prevent craniosynostosis in mice. International Journal of Oral Science. Accepted. https://sites.usc.edu/ccmb/files/2026/05/FGFR2-RA-Signaling-in-Craniosynostosis.pdf
Image: FGFR2-RA signaling governs dura mater-suture mesenchyme interaction during early postnatal development to control coronal suture development and craniosynostosis. Illustration created with BioRender.com.
New release: Bulk RNA-seq and Cut&Run-seq analysis of control and Gli1CreER;Kdm6bfl/fl adult mouse incisors
July 30th, 2026
A new bulk RNA-seq and Cut&Run-seq dataset from the University of Southern California is now available in FaceBase!
Contributors: Lin Meng, Mingyi Zhang, Jifan Feng, Tingwei Guo, Hana Hekmat, Heliya Ziaei, Peng Chen, Aaron Harouni, Thach-Vu Ho, Yang Chai (University of Southern California)
Description:
This study examined how mineralized tissues adapt to sustained mechanical stress, using mouse incisor models under varying degrees of loading. The data identify the histone demethylase KDM6B as an epigenetic regulator that preserves tissue homeostasis by protecting progenitor transit-amplifying cells from mechanical stress-induced apoptosis. Loss of Kdm6b increases H3K27me3 at the Bmi1 promoter, silencing Bmi1 and derepressing Piezo1, which drives excessive Ca2+ influx and apoptosis — while Piezo1 haploinsufficiency in Kdm6b-deficient mice rescues both the transit-amplifying cell defects and tissue homeostasis. Together the findings describe a KDM6B–H3K27me3–BMI1–PIEZO1 “mechanostat” that shields dental progenitor cells from mechanical stress. The dataset compares control and Gli1CreER;Kdm6bfl/fl adult mouse incisors by bulk RNA-seq and Cut&Run-seq.
FaceBase Dataset:
Lin Meng, Mingyi Zhang, Jifan Feng, Tingwei Guo, Hana Hekmat, Heliya Ziaei, Peng Chen, Aaron Harouni, Thach-Vu Ho, Yang Chai. Bulk RNA-seq and Cut&Run-seq analysis of control and Gli1CreER;Kdm6bfl/fl adult mouse incisors. FaceBase Consortium https://doi.org/10.25550/88-ZJCW (2026).
Publication:
Meng, L., Zhang, M., Feng, J., Guo, T., Hekmat, H., Ziaei, H., Chen, P., Harouni, A., Ho, T.-V., & Chai, Y. KDM6B safeguards mineralized tissue homeostasis from mechanical stress through epigenetic control of PIEZO1-mediated mechanotransduction in the mouse incisor. Bone Research 14(1), 59. https://doi.org/10.1038/s41413-026-00544-2 (2026).
Image: Schematic representation of KDM6B safeguarding tissue homeostasis to mechanical stress through epigenetic control of PIEZO1- mediated mechanotransduction. Using the mouse incisor as a model of mechanical loading, we reveal that within TACs, Kdm6b demethylates H3K27me3, thereby relieving the repression of the Bmi1 gene. Normal BMI1 inhibits Piezo1 expression. This maintains physiological PIEZO1 levels, ensuring calibrated Ca2+ influx for proliferation and differentiation. In contrast, loss of Kdm6b leads to an accumulation of H3K27me3 at the Bmi1 promoter region, which silences Bmi1 expression and diminishes BMI1 formation. This reduction results in pathologically increased PIEZO1 ion channels in the membrane. The subsequent Ca2+ overload triggers TAC apoptosis while reducing proliferation and differentiation. Ultimately, these molecular events compromise tissue homeostasis. Schematic created with BioRender.com. Ho, T. (2026) https://BioRender.com/8mzv4a3
Save the Date for the 2027 FaceBase Community Forum – April 27-28 in Los Angeles
July 13th, 2026
The 2027 FaceBase Community Forum will take place Tuesday, April 27 and Wednesday, April 28, 2027, in Los Angeles, CA (Marina del Rey), hosted at the USC Information Sciences Institute.
Tuesday will be a full day of programming; Wednesday will be a half day. Remote attendance via Zoom will also be available.
This gathering brings together dental, oral, and craniofacial (DOC) researchers, clinicians, and students - as well as those studying related biological systems (such as the ear and hearing research community) - working with FaceBase data and tools. An agenda, registration, and travel details will be announced in the coming months. Check back here or follow the link below for updates.
Check for updates: https://bit.ly/FBForum2027
New release: FGF signalling orchestrates multiple roles during salivary gland branching morphogenesis
May 26th, 2026
A new bulk RNA-seq dataset from King’s College London is now available in FaceBase!
Contributors: Abigail S. Tucker, Marta Perera, Joshua Brickman (King’s College London)
Description:
This study examined the role of the fibroblast growth factor (FGF) signalling pathway during branching morphogenesis in the murine embryonic submandibular salivary gland. The data compare pharmacological FGFR inhibition with conditional deletion of Fgfr2 (K14Cre;Fgfr2fl) from E13.5 +48 hours, revealing a multitude of roles for FGF signalling — including effects on fate decisions and tissue interactions. The dataset includes bulk RNA-Seq fastq files and the related counts matrix.
FaceBase Dataset:
Joshua Brickman, Abigail S. Tucker, Marta Perera. FGF signalling orchestrates multiple roles during salivary gland branching morphogenesis. FaceBase Consortium https://doi.org/10.25550/AH-J1XR (2026).
Image: Salivary gland stained with BrdU (proliferative cells, magenta) and DAPI (cyan). Image courtesy of Marta Perera.
New release: Amelogenin phosphorylation affects key regulatory genes in the enamel organ
April 30th, 2026A new amelogenin dataset is now available on FaceBase!
Contributors: Elia Beniash, Henry Margolis at the University of Pittsburgh (University of Pittsburgh)
Description:
Amelogenin (AMELX) is the predominant enamel matrix protein and has a single phosphorylation site at Serine 16 (S16), which enhances its ability to stabilize amorphous calcium phosphate in vitro. To investigate the in vivo role of AMELX phosphorylation, a knock-in mouse model (AmelxS16A) was generated in which S16 is substituted with Alanine to prevent phosphorylation. KI enamel is hypoplastic, lacks enamel rods, and features multiple ectopic calcifications; KI ameloblasts also lack Tomes’ processes and show progressive cell pathologies.
To characterize these effects comprehensively, single-cell RNA sequencing was performed on incisal enamel organs from WT and KI mice. 624 genes were differentially expressed across total enamel organ cell populations. Notably, Shh was downregulated 5.1-fold and Wnt5a was upregulated 8.1-fold in KI secretory ameloblasts compared to WT. Ten distinct cell populations were identified, with secretory ameloblasts showing the greatest transcriptomic impact, indicating that AMELX phosphorylation influences not only extracellular enamel matrix processes but also key intracellular pathways governing ameloblast biology.
FaceBase Dataset:
Elia Beniash, Henry Margolis. Amelogenin phosphorylation affects key regulatory genes in the enamel organ. FaceBase Consortium https://doi.org/10.25550/AF-V3VC (2026).