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

NATURE COMMUNICATIONS, 2021 · DOI: https://doi.org/10.1038/s41467-021-26321-9 · Published: October 14, 2021

Simple Explanation

Lizards can regrow their tails after amputation, but the new tail lacks the same detailed structure as the original, especially in the arrangement of skeletal tissues. This study investigates whether embryonic neural stem cells (NSCs), modified to be insensitive to certain signaling molecules, can improve tail regeneration in adult lizards. Researchers transplanted embryonic NSCs, which were genetically modified using CRISPR/Cas9 to knock out the smoothened (Smo) gene, into the regenerating tails of adult lizards. Smo is important for Hedgehog signaling. By implanting these modified NSCs, researchers aimed to restore the dorsoventral (top-bottom) patterning in the regenerated tails. The study found that the modified embryonic NSCs, when introduced into the adult lizard tails, opposed cartilage formation in dorsal regions and helped create a more structured, patterned tail skeleton. This suggests that embryonic NSCs can influence the regeneration process and improve the quality of the regrown tail.

Study Duration

4 Weeks

Participants

Lepidodactylus lugubris lizards

Evidence Level

Not specified

Key Findings

1
Embryonic NSCs transplanted into adult ETs lose roof plate identity and are ventralized by the unchecked Hedgehog signaling of adult lizard tail environments.
2
Embryonic lizard NSC lines unresponsive to Hedgehog stimulation are generated through the use of CRISPR/Cas9 technologies to knockout (KO) the signaling regulator smoothened (Smo).
3
Exogenous Smo KO NSCs injected into adult tail spinal cords engraft to endogenous ependymal cell populations and contribute to dorsal domains in regenerated tail ETs.

Research Summary

The study addresses the divergence between embryonic development and adult regeneration in lizard tails, particularly concerning skeletal tissue patterning and dorsoventral organization. Researchers used CRISPR/Cas9 gene editing to create embryonic neural stem cells (NSCs) unresponsive to Hedgehog signaling by knocking out the Smoothened (Smo) gene. The study demonstrates that Smo KO NSCs can maintain roof plate identities in vivo, leading to regenerated lizard tails with dorsoventrally patterned skeletal tissues and the formation of dorsal root ganglion (DRG)-like neural structures.

Practical Implications

Improved Regenerative Medicine

The research suggests methods for improving the quality and structure of regenerated tissues by manipulating stem cell differentiation and signaling pathways.

Understanding Evolutionary Trade-offs

The study sheds light on the trade-offs between cell plasticity and regenerative potential in amniotes, indicating how these processes can be influenced and potentially reversed.

Therapeutic Applications

The techniques developed in this study could potentially be adapted for therapeutic applications in tissue engineering and regenerative medicine, especially in cases where natural regeneration is limited or imperfect.

Study Limitations

1
Embryonic tails amputated in ovo (7 and 14 DPO) failed to regenerate.
2
Tails of embryos removed from eggs and cultured in vitro also failed to regrow following amputation, but this may have been an artifact of prolonged culture conditions.
3
Future work will focus on the functional ramiﬁcations of neurogenesis and skeletal pat- terning introduced to regenerated lizard tails.

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