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Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells

Author

Listed:
  • Thomas P. Lozito

    (University of Southern California
    University of Southern California)

  • Ricardo Londono

    (University of Pittsburgh School of Medicine)

  • Aaron X. Sun

    (University of Pittsburgh School of Medicine)

  • Megan L. Hudnall

    (University of Southern California)

Abstract

Lizards regenerate amputated tails but fail to recapitulate the dorsoventral patterning achieved during embryonic development. Regenerated lizard tails form ependymal tubes (ETs) that, like embryonic tail neural tubes (NTs), induce cartilage differentiation in surrounding cells via sonic hedgehog (Shh) signaling. However, adult ETs lack characteristically roof plate-associated structures and express Shh throughout their circumferences, resulting in the formation of unpatterned cartilage tubes. Both NTs and ETs contain neural stem cells (NSCs), but only embryonic NSC populations differentiate into roof plate identities when protected from endogenous Hedgehog signaling. NSCs were isolated from parthenogenetic lizard embryos, rendered unresponsive to Hedgehog signaling via CRISPR/Cas9 gene knockout of smoothened (Smo), and implanted back into clonally-identical adults to regulate tail regeneration. Here we report that Smo knockout embryonic NSCs oppose cartilage formation when engrafted to adult ETs, representing an important milestone in the creation of regenerated lizard tails with dorsoventrally patterned skeletal tissues.

Suggested Citation

  • Thomas P. Lozito & Ricardo Londono & Aaron X. Sun & Megan L. Hudnall, 2021. "Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26321-9
    DOI: 10.1038/s41467-021-26321-9
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    References listed on IDEAS

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    1. Martin Kragl & Dunja Knapp & Eugen Nacu & Shahryar Khattak & Malcolm Maden & Hans Henning Epperlein & Elly M. Tanaka, 2009. "Cells keep a memory of their tissue origin during axolotl limb regeneration," Nature, Nature, vol. 460(7251), pages 60-65, July.
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    Cited by:

    1. Ariel C. Vonk & Xiaofan Zhao & Zheyu Pan & Megan L. Hudnall & Conrad G. Oakes & Gabriela A. Lopez & Sarah C. Hasel-Kolossa & Alexander W. C. Kuncz & Sasha B. Sengelmann & Darian J. Gamble & Thomas P. , 2023. "Single-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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