# The Influence of Fluidic Flow Stress on the Development of the Secondary Palate

**Authors:** Masayo Nagata, Satoru Hayano, Ziyi Wang, Takahiro Kosami, Hiroshi Kamioka

PMC · DOI: 10.3390/jdb14010009 · Journal of Developmental Biology · 2026-02-12

## TL;DR

This study shows that mechanical stress from maternal movement helps develop the secondary palate in mice by promoting cell growth and bone formation.

## Contribution

The study reveals that exogenous fluidic flow stress enhances palatal development via Hippo and WNT/β-catenin pathways.

## Key findings

- Loaded palatal shelves showed increased thickness, volume, and cell proliferation.
- YAP and β-catenin nuclear translocation and osteogenic markers were upregulated in loaded tissues.
- No significant apoptosis was observed in response to mechanical stress.

## Abstract

Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate.

## Linked entities

- **Proteins:** YAP1 (Yes1 associated transcriptional regulator), ctnnb1.S (catenin beta 1 S homeolog), SP7 (Sp7 transcription factor), bglap2 (bone gamma-carboxyglutamate (gla) protein (osteocalcin) 2)
- **Diseases:** cleft palate (MONDO:0016064)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tafazzin (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 66826] {aka 5031411C02Rik, 9130012G04Rik, G4.5, Taz}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Wnt7b (wingless-type MMTV integration site family, member 7B) [NCBI Gene 22422] {aka Wnt-7b}, Lmnb1 (lamin B1) [NCBI Gene 16906], H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, Yap1 (yes-associated protein 1) [NCBI Gene 22601] {aka Yap, Yap65, Yki, Yorkie}, Shh (sonic hedgehog) [NCBI Gene 20423] {aka 9530036O11Rik, Dsh, HHG-1, Hhg1, Hx, Hxl3}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, Bglap2 (bone gamma-carboxyglutamate protein 2) [NCBI Gene 12097] {aka BGP2, Bglap1, Bgp, Og2, mOC-B}, Tgfb3 (transforming growth factor, beta 3) [NCBI Gene 21809] {aka TGF-beta-3, Tgfb-3}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Fgf10 (fibroblast growth factor 10) [NCBI Gene 14165] {aka AEY17, Fgf-10, Fgf5a, Gsfaey17}, Runx2 (runt related transcription factor 2) [NCBI Gene 12393] {aka AML3, CBF-alpha-1, Cbf, Cbfa-1, Cbfa1, LS3}, Ihh (Indian hedgehog) [NCBI Gene 16147] {aka HHG-2}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Cdh1 (cadherin 1) [NCBI Gene 12550] {aka ARC-1, E-cad, Ecad, L-CAM, UVO, Um}, Sp7 (Sp7 transcription factor 7) [NCBI Gene 170574] {aka 6430578P22Rik, C22, Osx}
- **Diseases:** orofacial clefts (MESH:C566121), necrosis (MESH:D009336), injury to (MESH:D014947), congenital malformations (OMIM:163000), Cleft lip and palate (MESH:D002971), Cleft palate (MESH:D002972), craniofacial birth defects (MESH:D019465)
- **Chemicals:** water (MESH:D014867), carbon dioxide (MESH:D002245), paraformaldehyde (MESH:C003043), sucrose (MESH:D013395), TBS (MESH:D013725), PVDF (MESH:C024865), SDS (MESH:D012967), ethanol (MESH:D000431), hyaluronic acid (MESH:D006820), Alexa Fluor  594 (-), aluminum (MESH:D000535), H-E (MESH:D006371), oxygen (MESH:D010100), Fluorescein (MESH:D019793), phosphotungstic acid (MESH:D010772), Hoechst  33342 (MESH:C017807), Triton X (MESH:D017830), Alexa Fluor  488 (MESH:C000711379)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12921741/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12921741/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921741/full.md

---
Source: https://tomesphere.com/paper/PMC12921741