Evidence map›Paper›PMID 40446216›Full record

ArticleDevelopment (Cambridge, England)2025

Distinct BMP-Smad signaling outputs confer diverse functions in dental mesenchyme.

Qinghuang Tang, Liwen Li, Yihong Li, Amy Wang, Hua Li, Linyan Wang, Cong Gu, Jung-Mi Lee, Zhaoming Wu, Hyuk-Jae Edward Kwon and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Qinghuang TangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.ORCID 0000-0002-9436-8628
Liwen LiDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Yihong LiFujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian Colleges and Universities, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350108, Fujian, P.R. China.
Amy WangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Hua LiDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Linyan WangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Cong GuDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Jung-Mi LeeDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA.
Zhaoming WuFaculty of Dentistry, The University of Hong Kong, Hong Kong SAR 000000, China.
Hyuk-Jae Edward KwonDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA.ORCID 0000-0001-6538-6045
YiPing ChenDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.ORCID 0000-0002-8628-7713

Funding

Genomic and functional investigations of the transcriptional regulatory network of tooth enamel developmentR01DE033085 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI Hyuk Jae Edward Kwon · 2023 to 2026
$2.5M
Role of BMP and Wnt signaling in early tooth developmentR01DE024152 · NIDCR · TULANE UNIVERSITY OF LOUISIANA · PI CHEN, YIPING · 2014 to 2018
$1.9M
NIDCR NIH HHS R01 DE024152NIDCR NIH HHS R01DE024152NIDCR NIH HHS R01 DE033085NIDCR NIH HHS R01DE033085NIH HHS R01DE024152NIH HHS R01DE033085
6 · The paper itself

Abstract

The canonical bone morphogenetic protein (BMP) signaling pathway plays a crucial regulatory role in tooth development by activating Smad proteins to regulate gene expression. We previously identified an atypical canonical BMP signaling in dental mesenchyme that is Smad4-independent but Smad1/5-dependent. This study demonstrates that phosphorylated Smad1/5 (pSmad1/5) and Smad4 regulate distinct gene sets in murine dental mesenchyme. Real-time monitoring of BMP-Smad transcriptional activity revealed that Smad4-dependent canonical BMP signaling is restricted to neurovascular cells surrounding the condensed dental mesenchymal cells where pSmad1/5 is present. Notably, pSmad1/5 in dental mesenchymal cells form complexes with pSmad3 to prevent canonical BMP signaling. CUT&RUN assays revealed genome-wide co-occupancy of pSmad1/5 and pSmad3, indicating their function as transcriptional regulation units. Integrative analyses demonstrated that this atypical canonical BMP signaling regulates tooth sensory innervation and maintains odontogenic inductive potential in dental mesenchyme, enabling the identification of crucial genes for maintaining tooth inductive capability. Our findings elucidate the operating mechanism of atypical canonical BMP signaling in dental mesenchymal cells and clarify how BMP-Smad signaling exerts diverse functions across different cell types, informing future tooth bioengineering strategies.

Indexed as

Bone Morphogenetic ProteinsMesodermSignal TransductionSmad ProteinsToothAnimalsGene Expression Regulation, DevelopmentalMiceOdontogenesisPhosphorylationSmad4 ProteinBone Morphogenetic ProteinsSmad4 ProteinSmad ProteinsAtypical canonical BMP-Smad signalingDental mesenchymeMouseOdontogenic inductive potentialTooth sensory innervation

Identifiers

PMID40446216
PMCPMC12211556

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.