# Prox1 maintains taste bud structure via inhibition of apoptosis

**Authors:** Aya Hagimoto, Eriko Koyanagi-Matsumura, Norihito Oura, Mitsuru Saito, Tatsurou Tanaka, Hirohito Miura

PMC · DOI: 10.1007/s00441-025-04040-7 · 2026-02-05

## TL;DR

Prox1 helps maintain taste bud structure by preventing cell death, ensuring proper function and longevity of taste cells.

## Contribution

This study reveals Prox1's novel role in taste bud homeostasis by inhibiting apoptosis and maintaining cell lifespan.

## Key findings

- Prox1 knockout mice had significantly fewer Type I, II, and III taste cells compared to wild-type mice.
- Apoptosis in taste bud cells nearly doubled in Prox1 knockout mice, reducing cell lifespan.
- Structural alterations in taste buds were observed due to increased apoptosis in Prox1 knockout mice.

## Abstract

Taste buds are maintained by continuous cell renewal, receiving a steady influx of postmitotic cells from the surrounding epithelial region. Within taste buds, Type I, II, and III cells continuously differentiate from Type IV postmitotic precursor cells and are removed via apoptosis. These processes are likely governed by various transcription factors. Among the transcription factors expressed in taste buds, Prox1, a homeobox transcription factor, is the only factor expressed in all taste bud cells including precursor cells. However, its role in taste buds remains unclear. Here, we investigate the function of Prox1 in taste bud cell turnover using conditional knockout (cKO) mice. In Prox1 cKO mice, all Type I, II, and III cells were significantly reduced, resulting in approximately half the total cell number per taste bud compared to wild-type mice, while Type IV cell numbers remained comparable. Apoptosis of taste bud cells nearly doubled, leading to a shortened lifespan of taste bud cells. EdU pulse-labeling experiments revealed a biphasic decline in EdU(+) taste bud cells in Prox1 cKO mice, indicating that Prox1 knockout increases the fraction of cells that die shortly after differentiating into taste bud cells. The surviving cells still exhibited a shorter lifespan than that of wild-type mice. We also observed previously unreported structural alterations within taste buds caused by enhanced apoptosis using whole-mount analysis. These results demonstrate that Prox1 contributes to the maintenance of taste bud structure by regulating the lifespan of taste bud cells, highlighting its essential role in taste bud homeostasis.

The online version contains supplementary material available at 10.1007/s00441-025-04040-7.

## Linked entities

- **Genes:** PROX1 (prospero homeobox 1) [NCBI Gene 5629]

## Full-text entities

- **Genes:** Tff2 (trefoil factor 2 (spasmolytic protein 1)) [NCBI Gene 21785] {aka SP, mSP}, Car4 (carbonic anhydrase 4) [NCBI Gene 12351] {aka Ca4}, Shh (sonic hedgehog) [NCBI Gene 20423] {aka 9530036O11Rik, Dsh, HHG-1, Hhg1, Hx, Hxl3}, Ascl1 (achaete-scute family bHLH transcription factor 1) [NCBI Gene 17172] {aka ASH1, Mash1, bHLHa46}, Itpr3 (inositol 1,4,5-triphosphate receptor 3) [NCBI Gene 16440] {aka IP3R 3, IP3R-3, Ip3r3, Itpr-3, tf}, Entpd2 (ectonucleoside triphosphate diphosphohydrolase 2) [NCBI Gene 12496] {aka Cd39l1, NTPDase2}, Cdkn1b (cyclin dependent kinase inhibitor 1B) [NCBI Gene 12576] {aka Kip1, p27, p27Kip1}, Kcnq1 (potassium voltage-gated channel, subfamily Q, member 1) [NCBI Gene 16535] {aka KVLQT1, Kcna9}, Pmaip1 (phorbol-12-myristate-13-acetate-induced protein 1) [NCBI Gene 58801] {aka Noxa}, Krt14 (keratin 14) [NCBI Gene 16664] {aka CK-14, K14, Krt-1.14, Krt1-14}, Snap25 (synaptosomal-associated protein 25) [NCBI Gene 20614] {aka Bdr, GENA70, SNAP-25, SUP, sp}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Nkx2-2 (NK2 homeobox 2) [NCBI Gene 18088] {aka Nkx-2.2, Nkx2.2, tinman}, Dntt (deoxynucleotidyltransferase, terminal) [NCBI Gene 21673] {aka Tdt}, Plcb2 (phospholipase C, beta 2) [NCBI Gene 18796] {aka B230205M18Rik, B230399N12}, Krt5 (keratin 5) [NCBI Gene 110308] {aka 3300001P10Rik, CK5, K5, Krt2-5, Tfip8}, Prox1 (prospero homeobox 1) [NCBI Gene 19130] {aka A230003G05Rik, PROX-1}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Bak1 (BCL2-antagonist/killer 1) [NCBI Gene 12018] {aka Bak, N-BAK1, N-Bak}, Etv1 (ets variant 1) [NCBI Gene 14009] {aka ER81, Etsrp81}, Pou2f3 (POU domain, class 2, transcription factor 3) [NCBI Gene 18988] {aka Epoc-1, Oct-11a, Oct11, Otf-11, Otf11, Skin}
- **Diseases:** hyperplasia (MESH:D006965), infection (MESH:D007239), tumor (MESH:D009369), embryonic lethality (MESH:D020964), tumorigenesis (MESH:D063646), colorectal carcinoma (MESH:D015179), dislocation (MESH:D004204)
- **Chemicals:** citrate (MESH:D019343), dUTP (MESH:C027078), Hoechst (-), EdU (MESH:C022811), TBS (MESH:D013725), sodium (MESH:D012964), TO-PRO-3 (MESH:C098830), Tween 20 (MESH:D011136), TE (MESH:D013691), PFA (MESH:C003043), Triton X-100 (MESH:D017830), Hoechst 33342 (MESH:C017807), EDTA (MESH:D004492)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872690/full.md

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Source: https://tomesphere.com/paper/PMC12872690