Genetic Reprogramming of Positional Memory in a Regenerating Appendage.

Journal Article (Journal Article)

Certain vertebrates such as salamanders and zebrafish are able to regenerate complex tissues (e.g., limbs and fins) with remarkable fidelity. However, how positional information of the missing structure is recalled by appendage stump cells has puzzled researchers for centuries. Here, we report that sizing information for adult zebrafish tailfins is encoded within proliferating blastema cells during a critical period of regeneration. Using a chemical mutagenesis screen, we identified a temperature-sensitive allele of the gene encoding DNA polymerase alpha subunit 2 (pola2) that disrupts fin regeneration in zebrafish. Temperature shift assays revealed a 48-h window of regeneration, during which positional identities could be disrupted in pola2 mutants, leading to regeneration of miniaturized appendages. These fins retained memory of the new size in subsequent rounds of amputation and regeneration. Similar effects were observed upon transient genetic or pharmacological disruption of progenitor cell proliferation after plucking of zebrafish scales or head or tail amputation in amphioxus and annelids. Our results provide evidence that positional information in regenerating tissues is not hardwired but malleable, based on regulatory mechanisms that appear to be evolutionarily conserved across distantly related phyla.

Full Text

Duke Authors

Cited Authors

  • Wang, Y-T; Tseng, T-L; Kuo, Y-C; Yu, J-K; Su, Y-H; Poss, KD; Chen, C-H

Published Date

  • December 16, 2019

Published In

Volume / Issue

  • 29 / 24

Start / End Page

  • 4193 - 4207.e4

PubMed ID

  • 31786062

Pubmed Central ID

  • PMC6917923

Electronic International Standard Serial Number (EISSN)

  • 1879-0445

Digital Object Identifier (DOI)

  • 10.1016/j.cub.2019.10.038


  • eng

Conference Location

  • England