1. Developmental Biology
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Regeneration of the larval sea star nervous system by wounding induced respecification to the sox2 lineage

  1. Minyan Zheng
  2. Olga Zueva
  3. Veronica Hinman  Is a corresponding author
  1. Harvard Medical School, United States
  2. Carnegie Mellon University, United States
Research Article
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Cite this article as: eLife 2022;11:e72983 doi: 10.7554/eLife.72983


The ability to restore lost body parts following traumatic injury is a fascinating area of biology that challenges current understanding of the ontogeny of differentiation. The origin of new cells needed to regenerate lost tissue, and whether they are pluripotent stem cells, tissue-specific stem cells or have de- or trans- differentiated, remains one of the most important open questions in regeneration. Additionally, it is not clearly known whether developmental gene regulatory networks (GRNs) are reused to direct specification in these cells or whether regeneration specific networks are deployed. Echinoderms, including sea stars, have extensive ability for regeneration and have therefore been the subject of many thorough studies on the ultrastructural and molecular properties of cells needed for regeneration. However, the technologies for obtaining transgenic echinoderms are limited and tracking cells involved in regeneration, and thus identifying the cellular sources and potencies has proven challenging. In this study we develop new transgenic tools to follow the fate of populations of cells in the regenerating bipinnaria larva of the sea star Patira minaita. We show that the larval serotonergic nervous system can regenerate following decapitation. Using a BAC-transgenesis approach with photoconvertible fluorescent proteins, we show that expression of the pan ectodermal marker, sox2, is induced in previously sox2 minus cells at the wound site, even when cell division is inhibited. sox2+ cells give rise to new sox4+ neural precursors that then proceed along an embryonic neurogenesis pathway to reform the anterior nervous systems. sox2+ cells contribute to only neural and ectoderm lineages, indicating that these progenitors maintain their normal, embryonic lineage restriction. This indicates that sea star larval regeneration uses a combination of existing lineage restricted stem cells, as well as respecification of cells into neural lineages, and at least partial reuse of developmental GRNs to regenerate their nervous system.

Data availability

All data generated in this study are included in the manuscript. Genomic sequence data is provided with accessing numbers and/or links to Echinobase.org

Article and author information

Author details

  1. Minyan Zheng

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7990-1773
  2. Olga Zueva

    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Veronica Hinman

    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3414-1357


National Science Foundation (NSF. IOS 1557431)

  • Veronica Hinman

National Institute of General Medical Sciences (NIH 1R24OD023046)

  • Veronica Hinman

DSF Charitable Foundation

  • Veronica Hinman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Phillip A Newmark, Morgridge Institute for Research, United States

Publication history

  1. Received: August 11, 2021
  2. Accepted: January 13, 2022
  3. Accepted Manuscript published: January 14, 2022 (version 1)


© 2022, Zheng et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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