# The planarian dorsal–ventral boundary regulates anterior–posterior axis growth and patterning

**Authors:** Chloe L. Maybrun, Isaac M. Oderberg, Michael A. Gaviño, Thomas F. Cooke, Kyungyong Choi, Jongyoon Han, Peter W. Reddien, Richard Hodge, Richard Hodge, Richard Hodge, Richard Hodge

PMC · DOI: 10.1371/journal.pbio.3003482 · 2025-11-11

## TL;DR

This study shows how the dorsal-ventral boundary in planarians controls the growth and patterning of the front-back body axis during regeneration.

## Contribution

The study reveals a hierarchical model where the dorsal-ventral boundary directs anterior-posterior axis formation during regeneration.

## Key findings

- The dorsal-ventral boundary (DVB) is necessary and sufficient for anterior-posterior axis growth in low Wnt conditions.
- Ectopic DVB can induce head formation at experimentally dictated locations after Wnt inhibition.
- DVB removal blocks anterior positional information during head regeneration.

## Abstract

Regeneration can involve the coordination of pattern formation in an outgrowth with the spatial pattern of pre-existing tissues, such as along body axes. Planarian adult axis patterning serves as a robust context for uncovering the mechanisms of such pattern integration. We investigated how the dorsal–ventral boundary (DVB), which surrounds the animal periphery at the dorsal–ventral (DV) median plane, regulates anterior–posterior (AP) axis growth and patterning. We define a spatial DVB gene expression atlas that includes genes encoding signaling, adhesion, and transcription factors. Wnt inhibition results in anterior positional information induction and ectopic head formation that is restricted to the DVB. DVB can be transplanted, and DVB identity can be experimentally induced at ectopic locations. Ectopic DVB is competent for anterior positional identity induction following Wnt inhibition, enabling the generation of animals with ectopic heads at experimentally dictated locations. DVB removal blocks the anteriorization that normally follows Wnt inhibition and prevents anterior positional information expression during head regeneration. Anterior positional information induction at the DVB after Wnt inhibition occurs independently from anterior pole formation, which promotes head patterning in regeneration. Our findings reveal a hierarchical model of pattern integration across body axes in which DV patterning is central by producing a DVB with competence to direct formation of large AP axis regions. This mechanism enables coordination of orthogonal positional information in the context of regeneration.

Regeneration in planarians requires alignment of new tissue axes with existing body axes. This study shows that such pattern integration is coordinated by the dorsal–ventral boundary (DVB). The DVB is necessary and sufficient for anterior–posterior axis outgrowth and patterning in a low Wnt environment.

## Full-text entities

- **Genes:** Pxd (Peroxidase) [NCBI Gene 2768671] {aka CG3477, DmPO, Dmel\CG3477, Dpxd, HPX1, PO}, ctnnb1.L (catenin beta 1 L homeolog) [NCBI Gene 399274] {aka B-catenin, beta-catenin, ctnnb, ctnnb1, ctnnb1-a, ctnnb1-b}, Src64B (Src oncogene at 64B) [NCBI Gene 48973] {aka C-src1, CG7524, D-Src64B, D-src, DSRC64, DSrc}, Notum (notum) [NCBI Gene 39751] {aka CG13076, Dmel\CG13076, Not, Nt, Wf, anon-WO0118547.482}, Dsor1 (Downstream of raf1) [NCBI Gene 31872] {aka CG15793, D-MEK, D-MEK/Dsor, D-Mek, D-SOR, D-Sor}, gsk3b.L (glycogen synthase kinase 3 beta L homeolog) [NCBI Gene 399097] {aka gsk-3, gsk3, gsk3-beta, gsk3b, gsk3beta, xgsk-3}, tin (tinman) [NCBI Gene 42536] {aka CG7895, DROHOXHK4, DROHOXNK4, DmNK-4, Dmel\CG7895, HOX}, ninaE (neither inactivation nor afterpotential E) [NCBI Gene 42367] {aka 143283_at, 1F9, BEST:GH11778, CG4550, DMELRH1, DRh1}, fd59A (forkhead domain 59A) [NCBI Gene 37631] {aka CG3668, Dmel\CG3668, Dmfd3, FD3, FoxD, fd3}, Eph (Eph receptor tyrosine kinase) [NCBI Gene 43803] {aka CG1511, CT3831, DEK, Dek, Dek7, Deph}, nau (nautilus) [NCBI Gene 42799] {aka CG10250, Dmel\CG10250, Dmyd, MYOD, Mdrf, MyoD}, Lam (Lamin) [NCBI Gene 33782] {aka 2459, 74/76, CG6944, D5, DM[[O]], D[[m0]]}, Pc (Polycomb) [NCBI Gene 40358] {aka CG32443, CG7618, DmPc, Dmel\CG32443, Pc-G, PcG}, rl (rolled) [NCBI Gene 3354888] {aka 12559, BcDNA:RE08694, CG12559, CG18732, CT34260, CT39192}, unc-22 (Twitchin;non-specific serine/threonine protein kinase) [NCBI Gene 178135], smad1.S (SMAD family member 1 S homeolog) [NCBI Gene 399457] {aka MLP, XMad, Xmad1, Xsmad1, madh1, smad-1}, Wnt5 (Wnt oncogene analog 5) [NCBI Gene 32838] {aka CG6407, DWnt-3, DWnt-3/5, DWnt-5, DWnt3, DWnt3/5}, dpp (decapentaplegic) [NCBI Gene 33432] {aka BMP, Bmp, CG9885, DPP-C, Dm-DPP, DmDPP}, Smox (Smad on X) [NCBI Gene 31738] {aka CG2262, DSMAD2, DSmad2, Dmel\CG2262, SMAD2, Sad}, Fs (Follistatin) [NCBI Gene 2768836] {aka CG12955, CG12956, CG33466, Dmel\CG33466, Fol1, dFS}, N (Notch) [NCBI Gene 31293] {aka 1.1, 16-178, 16-55, Ax, CG3936, CT13012}, wg (wingless) [NCBI Gene 34009] {aka Br, CG4889, D.int-1, DWint-1, DWnt-1, Dint-1}
- **Diseases:** PCGs (MESH:C536209), UMAP (MESH:C567162), injuries (MESH:D014947)
- **Chemicals:** MgCl2 (MESH:D015636), MgSO4 (MESH:D008278), Holtfreter (-), DNP (MESH:D019297), PD (MESH:C506614), calcium (MESH:D002118), magnesium (MESH:D008274), glucose (MESH:D005947), phospholipids (MESH:D010743), PBS (MESH:D007854), trypan blue (MESH:D014343), KCl (MESH:D011189), water (MESH:D014867), NaCl (MESH:D012965), HEPES (MESH:D006531), DMSO (MESH:D004121), CaCl2 (MESH:D002122), EDTA (MESH:D004492), NaHCO3 (MESH:D017693), ethanol (MESH:D000431), sodium azide (MESH:D019810), Triton-X (MESH:D017830), FITC (MESH:D016650), chloretone (MESH:D002724)
- **Species:** C. elegans [taxon 328850], Xenopus laevis (African clawed frog, species) [taxon 8355], Ambystoma mexicanum (axolotl, species) [taxon 8296], Planaria (genus) [taxon 1292361], Danio rerio (leopard danio, species) [taxon 7955], Schmidtea mediterranea (freshwater planarian, species) [taxon 79327], Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227], Caudata (salamanders, order) [taxon 8293], Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** 4D, S2H, S4D, S6C, S1C, S2, S1, 4 C

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12629446/full.md

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Source: https://tomesphere.com/paper/PMC12629446