Articles & Events

New release: Sensory nerve-derived signaling coordinates oropharyngeal structural organization that supports suckling and vocalization in neonatal mice

A new dataset from the Chai lab at the University of Southern California is now available in FaceBase, combining single-cell RNA sequencing, bulk RNA sequencing, and SeqFISH spatial transcriptomics to examine how sensory nerves shape the developing soft palate.

Contributors: Sa Cha, Jifan Feng, Tingwei Guo, Lin Meng, Peng Chen, Calista Ly, Thach-Vu Ho (Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California); Pedro A. Sanchez-Lara (Section of Medical Genetics, Department of Pediatrics, Guerin Children’s at Cedars-Sinai Medical Center); Lauren E. McElvain and Jeffrey D. Moore (Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California); Yang Chai (Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California)

Description:

Proper oropharyngeal function is essential for suckling, feeding, and speech, and relies on the coordinated development of the palate, oropharyngeal musculature, and the cranial nerves that control them. Disruption of this integration leads to severe neonatal complications. However, how neuromuscular architecture is developmentally coordinated to support oropharyngeal function remains unclear. Using single-cell and spatial transcriptomics, we identify trigeminal nerve-derived GDF11 as a crucial regulator of soft palatal muscle architecture that acts through cranial neural crest-derived perimysial cells and is mediated by Akt-FoxO1-Thbs3 signaling to establish muscle structural integrity and bilateral continuity. To assess its functional relevance in vivo, we employ a battery of physiological assays to evaluate oropharyngeal function in neonatal mice and find that sensory neuron-specific Gdf11 deletion recapitulates soft palatal deformities and associated oropharyngeal dysfunction observed in individuals carrying GDF11 mutations, including impaired suckling, reduced oropharyngeal motor efficacy, and abnormal vocalizations. Pharmacological activation of AKT partially restores soft palatal muscle organization and ameliorates associated physiological deficits in Gdf11 mutant mice. Collectively, these findings demonstrate that sensory nerve-derived trophic signaling is indispensable for coordinated oropharyngeal morphogenesis and function, and establish a pre-clinical framework for the therapeutic approach targeting neuromuscular integration in congenital oropharyngeal disorders.

What’s in the dataset

The deposited data are embryonic. Samples come from trigeminal ganglion and palatal shelf tissue at E13.5 and E14.5, spanning eight experiments, 19 biosamples, and more than 25 files. Three assay types are represented:

• Single-cell RNA sequencing of dissected tissue
• Bulk RNA sequencing
• SeqFISH spatial transcriptomics, preserving positional information across the palatal shelves

Processing used Cell Ranger 9.0.0 and SGNlite, with sequencing on Illumina NextSeq 500 and NovaSeq platforms.

The data are open access and can be downloaded directly from FaceBase.

This work was supported by NIDCR grants R01 DE012711 and U01 DE028729 to Yang Chai. The U01 is a FaceBase data generation project, making this a case of FaceBase-funded research depositing its underlying data back into the repository.

FaceBase Dataset:

Sa Cha, Jifan Feng, Tingwei Guo, Lin Meng, Peng Chen, Calista Ly, Thach-Vu Ho, Pedro Sanchez, Lauren E. McElvain, Jeffrey D. Moore, Yang Chai. Investigating Oropharyngeal Development in Neonatal Mice Using scRNA sequencing, RNA sequencing, and SeqFISH. FaceBase Consortium https://doi.org/10.25550/8N-FGKC (2026).

Associated Publication:

Cha S, Feng J, Guo T, Meng L, Chen P, Ly C, Ho TV, Sanchez-Lara PA, McElvain LE, Moore JD, Chai Y. Sensory nerve-derived signaling coordinates oropharyngeal structural organization that supports suckling and vocalization in neonatal mice. Nat Commun. 2026 Jul 14. Advance online publication. https://doi.org/10.1038/s41467-026-74959-0

New release: Center for TMD IMPACT (C-TMD IMPACT) Patient and Clinician Needs Assessment

Two new datasets from the Center for TMD IMPACT (C-TMD IMPACT) are now available in FaceBase. Together, they offer a view of common needs and common barriers from both sides of the clinical encounter, and a starting point for researchers and clinicians looking to collaborate on addressing TMDs.

Contributors: Yang Chai, Jian-Fu Chen, and VyVy Nguyen (University of Southern California)

Description:

During the TMD IMPACT Collaborative R34 planning phase, the Center for TMD IMPACT at the University of Southern California conducted a needs assessment to better understand the needs of patients who experience symptoms of TMD and clinicians who treat them. Both surveys were administered in 2024 and the resulting data have been de-identified for open release.

Patient Needs Assessment

Center for TMD IMPACT Patient Needs Assessment includes survey responses from 103 patients seen at the USC Orofacial Pain and Oral Medicine Center between May and July 2024. The survey covered patient demographics, descriptions of symptoms, and descriptions of treatments. Patients identified six priority areas for improving TMD treatment: better coverage of treatment, faster and more immediate access to care, more frequent appointments, better information about TMD, more knowledgeable providers, and better bedside manner from clinicians.

Clinician Needs Assessment

Center for TMD IMPACT Clinician Needs Assessment includes survey responses from 17 practicing clinicians in the Los Angeles and San Francisco Bay areas who treat patients with TMDs, collected between June and August 2024. The survey covered clinician demographics, opinions on the current standard of treatment, and ideas for improving it. Clinicians pointed to three priority areas: addressing gaps in phenotyping and pain research, improving patient access to care, and improving quality of care through interdisciplinary practice, better educational curriculum and opportunities, and better technology and software.

Each dataset includes the survey response data, a data dictionary, and a PDF of the survey instrument. Both are open access under General Research Use (GRU) limitations and can be downloaded directly from FaceBase.

FaceBase Datasets:

Yang Chai, Jian-Fu Chen, VyVy Nguyen. Center for TMD IMPACT Patient Needs Assessment. FaceBase Consortium https://doi.org/10.25550/9N-634P (2026).

Yang Chai, Jian-Fu Chen, VyVy Nguyen. Center for TMD IMPACT Clinician Needs Assessment. FaceBase Consortium https://doi.org/10.25550/9N-634W (2026).

New release: Temporally regulated FGFR2–retinoic acid signaling mediates dura mater–suture mesenchyme interactions to prevent craniosynostosis in mice

A 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 Fgfr2^IIIc 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 Fgfr2^IIIc mutant mice, confirming retinoic acid signaling as a key downstream effector of FGFR2 signaling. Notably, restoration of suture patency alone rescues neurocognitive dysfunctions in Fgfr2^IIIc 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

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

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