Evidence map›Paper›PMID 40391979›Full record

ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2025

Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face.

Nicholas Hanne, Diane Hu, Marta Vidal-García, Charlie Allen, M Bilal Shakir, Wei Liu, Benedikt Hallgrímsson, Ralph Marcucio

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental dynamics : an official publication of the American Association of Anatomists, 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. Three-dimensional cellular dynamics and mandibular morphogenesis.Frontiers in cell and developmental biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Nicholas HanneDepartment of Orthopaedic Surgery, University of California-San Francisco, San Francisco, California, USA.ORCID 0000-0002-3715-6768
Diane HuDepartment of Orthopaedic Surgery, University of California-San Francisco, San Francisco, California, USA.
Marta Vidal-GarcíaDeptartment of Cell Biology & Anatomy, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Charlie AllenCardiovascular Research Institute, University of California-San Francisco, San Francisco, California, USA.
M Bilal ShakirDeptartment of Cell Biology & Anatomy, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Wei LiuDeptartment of Cell Biology & Anatomy, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Benedikt HallgrímssonDeptartment of Cell Biology & Anatomy, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Ralph MarcucioDepartment of Orthopaedic Surgery, University of California-San Francisco, San Francisco, California, USA.

Funding

The role of continuous phenotypic variation in structural defects of the faceR01DE019638 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Benedikt Hallgrimsson, Ralph S Marcucio · 2010 to 2026
$7.3M
Canada First Research Excellence Fund 2022-00015Canada Foundation for Innovation 36262CIHR 159920Natural Sciences and Engineering Research Council of Canada 238992-2NIDCR NIH HHS F32-DE030359NIDCR NIH HHS R01 DE019638NIDCR NIH HHS R01-DE019638
6 · The paper itself

Abstract

backgroundPreviously we found that increasing fibroblast growth factor (FGF) signaling in the neural crest cells within the frontonasal process (FNP) of the chicken embryo caused dysmorphology that was correlated with reduced proliferation, disrupted cellular orientation, and lower MAPK activation but no change in PLCγ and PI3K activation. This suggests RTK signaling may drive craniofacial morphogenesis through specific downstream effectors that affect cellular activities. In this study we inhibited three downstream branches of RTK signaling to determine their role in regulating cellular activities and how these changes affect morphogenesis of the FNP.

resultsSmall molecule inhibitors of MEK1/2, PI3K, and PLCγ were delivered individually and in tandem to the right FNP of chicken embryos. All treatments caused asymmetric proximodistal truncation on the treated side and a mild expansion on the untreated side compared to DMSO control treated FNPs. Inhibiting each pathway caused similar decreased proliferation and disrupted cellular orientation, and only mildly increased apoptosis.

conclusionsSince RTK signaling is a ubiquitous and tightly regulated biochemical system, we conclude that the downstream pathways are robust to developmental perturbation through redundant signaling systems.

Indexed as

FaceMorphogenesisReceptor Protein-Tyrosine KinasesSignal TransductionAnimalsCell ProliferationChick EmbryoNeural CrestPhosphatidylinositol 3-KinasesPhosphatidylinositol 3-KinasesReceptor Protein-Tyrosine Kinasescellular activitycraniofacialmorphogenesistyrosine kinase signaling

Identifiers

PMID40391979
PMCPMC13178690

What OpenQuestion holds

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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 OpenQuestion graph.