Biology subjects

Taniguchi-Sugiura, Y.

Publications and source records attributed to Taniguchi-Sugiura, Y..

5 recordsLinked to original sources

bioRxiv2026

Adult regenerative defects arise from discordant scaling of signal dependent growth and patterning

Orders of magnitude distinguish an organs size in adulthood from its size when patterning was established during embryonic development. The prospect of engineering adult organ regeneration raises the fundamental question of whether regenerative stem cell patterning should be elicited at embryonic or adult scale. Axolotls regenerate their limbs at all stages of post-embryonic life, encompassing an order of magnitude increase in animal size, but the mechanisms allowing this robust capacity remain unclear. Limb regeneration occurs by the formation of an embryonic-like progenitor zone, the blastema, whose dimensions increase with animal size, suggesting that at least some aspects of limb regeneration must scale. Here, by combining spatial transcriptomics, biophysical modelling, quantitative imaging, and functional perturbations, we found distinct scaling signatures among key signaling pathways, arguing against a body-size-dependent hormonal scaling mechanism. SHH signaling showed partial scaling that saturated in largest adult sizes, with a correspondingly early termination of blastema growth while Wnt9a-modulated digit patterning scaled at all animal sizes. As a result of this differential scaling, digit patterning wavelength was mismatched with respect to domain growth in the largest blastemas, preventing the addition of the last digit. In agreement with this model, regenerative failure can be rescued by timed supplementation of SHH. Our results show that coordinated scaling of morphogen signaling is a key requirement for adult organ regeneration.

systems biology↗

bioRxiv2025

AXL governs axolotl cardiac regeneration and directs mammalian cardiomyocyte dedifferentiation

Cardiac injury outcomes vary widely across species, from complete regeneration to irreversible scarring. Using single-nucleus multiomics and spatial transcriptomics, we generated a spatially resolved atlas of axolotl heart regeneration following injury, identifying a distinct border-zone cardiomyocyte population with a pro-regenerative transcriptional program. Ligand-receptor analysis of the border zone niche identified enrichment of the receptor tyrosine kinase AXL in injury-responsive cardiomyocytes and its ligand Gas6 in endothelial cells. Functional perturbation demonstrated AXL requirement for border-zone cardiomyocyte activation and axolotl heart regeneration. In murine cardiomyocytes, AXL overexpression induced sarcomere disassembly, metabolic rewiring, and immature gene expression without triggering proliferation. These findings show that AXL signaling induces cardiomyocyte dedifferentiation and uncouples dedifferentiation from cell cycle re-entry, providing mechanistic insight into cellular plasticity during heart regeneration.

cell biology↗

bioRxiv2024

Somite-independent regeneration of the axolotl primary body axis

Primary body-axis development is a highly conserved process that proceeds through somitogenesis and subsequent subdivision into dermatome, myotome, and sclerotome. Defects in somitic-clock genes such as Hes7 lead to vertebral-segmentation defects in mice and fish. Here we show that in the axolotl, although Hes7 is necessary for proper embryonic vertebral segmentation, it is-- surprisingly--dispensable during tail regeneration. We investigated the mechanism of vertebral segmentation during regeneration which initially occurs through extension of a cartilage rod ventral to the spinal cord. We find that the regenerating cartilage rod undergoes a periodic wrinkling that provides a template for vertebral segmentation. Via direct mechanical measurements and biophysical perturbations, we show that a model of compression-induced buckling instability can predict vertebral segmentation. The cartilage rod and other somitic derivatives (muscle, cartilage, tendon, fibroblasts) arise from tendon-like, Lfng+ multi-potent mesenchymal progenitors, which display a gene regulatory state distinct from somitic progenitors. In summary, we uncover a mechanism of vertebral segmentation during axolotl tail regeneration that is distinct from the somite-based developmental mechanism.

developmental biology↗

bioRxiv2023

Molecular basis for positional memory and its reprogrammability in limb regeneration

Upon limb amputation in salamanders, anterior and posterior connective tissue cells form distinct signalling centres that together fuel successful regeneration. The molecular properties that distinguish anterior and posterior cells prior to injury, which enable them to initiate different signalling centres after amputation, are not known. These anterior and posterior identities, crucial for regeneration, were thought to be established during development and to persist through successive regeneration cycles as positional memory. However, the molecular nature of these memory states and whether these identities can be engineered have remained outstanding questions. Here, we identify a positive feedback mechanism encoding posterior identity in the axolotl limb, which can be used to newly encode positional memory in regenerative cells. Posterior cells express residual levels of the bHLH transcription factor Hand2 from development and this is a priming molecule necessary and sufficient to establish a Shh signalling centre after limb amputation. During regeneration, Shh feeds back and reinforces Hand2 expression in nearby cells. Hand2 is sustained following regeneration, safeguarding posterior memory, while Shh is shut off. As a consequence of this Hand2-Shh system, anterior and posterior identities are differentially susceptible to alteration. Posterior cells are stabilised against anteriorisation as their expression of Hand2 poises them to trigger the Hand2-Shh loop. In contrast, anterior cells can be reprogrammed: a transient exposure to Shh during regeneration causes anterior cells to gain Hand2 expression and a lasting competence to express Shh. In this way, regeneration is an opportunity and entry point to re-write positional memory. Our results implicate positive feedback in the stability of positional memory and explain why positional memory is more easily altered in one direction (anterior to posterior) than the other. Because modifying positional memory changes signalling outputs from regenerative cells, our findings have wider implications for tissue engineering.

developmental biology↗

bioRxiv2022

Chromatin states at homeoprotein loci distinguish axolotl limb segments prior to regeneration

The salamander limb regenerates only the missing portion. Each limb segment can only form segments equivalent to- or more distal to their own identity, relying on a property termed "positional information". How positional information is encoded in limb cells has been unknown. By cell-type-specific chromatin profiling of upper arm, lower arm, and hand, we found segment-specific levels of histone H3K27me3 at limb homeoprotein gene loci but not their upstream regulators, constituting an intrinsic segment information code. During regeneration, regeneration-specific regulatory elements became active prior to the re-appearance of developmental regulatory elements. This means that, in the hand segment, the permissive chromatin state of the hand homeoprotein gene HoxA13 engages with regeneration regulatory elements, bypassing the upper limb program.

developmental biology↗