# Making Mobile Leaflets: Biomechanical Forces in Atrioventricular Valve Formation

**Authors:** Anji Yang, Renee Wei-Yan Chow

PMC · DOI: 10.3390/cells15060562 · 2026-03-20

## TL;DR

This paper explores how biomechanical forces guide the development of heart valves, focusing on the steps that can lead to valve disease if disrupted.

## Contribution

The paper provides a comparative review of in vivo models to understand biomechanical regulation in atrioventricular valve formation.

## Key findings

- Biomechanical forces are critical across multiple stages of atrioventricular valve development.
- Endocardial cushion formation and extracellular matrix remodeling are influenced by hemodynamic cues.
- Comparative analysis of in vivo models reveals shared and distinct regulatory mechanisms.

## Abstract

Atrioventricular valves prevent the backward flow of blood from the ventricles to the atria and are essential for the efficient pumping of blood throughout the body. Errors in development can lead to congenital atrioventricular valve disease. Atrioventricular valve formation is a multi-step process that involves endocardial cushion formation, valve progenitor cell proliferation, valve sinus formation, valve elongation, and extracellular matrix remodeling. Increasing evidence suggests that hemodynamic cues are required across multiple steps. Here, we compare atrioventricular valve formation in different in vivo models and review how biomechanical forces regulate atrioventricular valve formation.

## Full-text entities

- **Genes:** Egr3 (early growth response 3) [NCBI Gene 13655] {aka EGR-3, Pilot}, tnnt2a (troponin T type 2a (cardiac)) [NCBI Gene 58071] {aka cTnT, ctnnt, tnnt2}, Gata1 (GATA binding protein 1) [NCBI Gene 14460] {aka Gata-1, Gf-1, eryf1}, Notch1 (notch 1) [NCBI Gene 18128] {aka 9930111A19Rik, Mis6, N1, Tan1, lin-12}, Nfatc3 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 3) [NCBI Gene 18021] {aka D8Ertd281e, NFAT4, NFATx}, Wnt9a (wingless-type MMTV integration site family, member 9A) [NCBI Gene 216795] {aka Wnt14, wnt-14}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Nfatc4 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4) [NCBI Gene 73181] {aka 3110041H08Rik, Nfat3}, Piezo1 (piezo-type mechanosensitive ion channel component 1) [NCBI Gene 234839] {aka 9630020g22, Fam38a, mKIAA0233}, Snai2 (snail family zinc finger 2) [NCBI Gene 20583] {aka Slug, Slugh, Snail2}, Snai1 (snail family zinc finger 1) [NCBI Gene 20613] {aka Sna, Sna1, Snail, Snail1}, Yap1 (yes-associated protein 1) [NCBI Gene 22601] {aka Yap, Yap65, Yki, Yorkie}, Mapk7 (mitogen-activated protein kinase 7) [NCBI Gene 23939] {aka BMK-1, BMK1, ERK-5, ERK5, Erk5-T, PRKM7}, Cacnb2 (calcium channel, voltage-dependent, beta 2 subunit) [NCBI Gene 12296] {aka CAB2, Cavbeta2, Cchb2}, Wnt9b (wingless-type MMTV integration site family, member 9B) [NCBI Gene 22412] {aka Wnt14b, Wnt15, clf, clf1, wnt-14b, wnt-15}, Klf2 (Kruppel-like transcription factor 2 (lung)) [NCBI Gene 16598] {aka Lklf}, KLF2 (Kruppel like factor 2) [NCBI Gene 420148], Eln (elastin) [NCBI Gene 13717] {aka E030024M20Rik}, Ttn (titin) [NCBI Gene 22138] {aka 1100001C23Rik, 2310036G12Rik, 2310057K23Rik, 2310074I15Rik, D330041I19Rik, D830007G01Rik}, Eng (endoglin) [NCBI Gene 13805] {aka CD105, Endo, S-endoglin}, Dll4 (delta like canonical Notch ligand 4) [NCBI Gene 54485] {aka Delta4}, cdh5 (cadherin 5) [NCBI Gene 445471] {aka fc88a07, mlb, wu:fc88a07}, Nfatc1 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1) [NCBI Gene 18018] {aka 2210017P03Rik, NF-ATc, NFAT2, NFATc, Nfatcb}, Klf4 (Kruppel-like transcription factor 4 (gut)) [NCBI Gene 16600] {aka EZF, Gklf, Zie}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}
- **Diseases:** PKD (MESH:C537180), injury to (MESH:D014947), aortic valve disease (MESH:D000082862), tricuspid stenosis (MESH:D014264), Atrioventricular Valves (MESH:D006349), embryonic lethality (MESH:D020964), congenital heart defects (MESH:D006330), tricuspid atresia (MESH:D018785), mitral stenosis (MESH:D008946), Ebstein anomaly (MESH:D004437), ventricular systole (MESH:D018487), valve stenosis (MESH:D001024), mitral insufficiency (MESH:D008944)
- **Chemicals:** oxygen (MESH:D010100), calcium (MESH:D002118), Ca2+ (-), hyaluronic acid (MESH:D006820), dofetilide (MESH:C063533), water (MESH:D014867), cyclosporine (MESH:D016572), ATP (MESH:D000255)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Gallus gallus (bantam, species) [taxon 9031]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025464/full.md

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Source: https://tomesphere.com/paper/PMC13025464