# Why don’t lizards regenerate perfect tails like salamanders?

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $346,500

## Abstract

Enhancing regenerative capacities is a fundamental goal in medicine. As yet, the principles of salamander
regeneration to augment mammalian healing are not directly applicable. Here we propose using lizards, more
closely related to mammals yet exhibiting remarkable regenerative capabilities, as model organisms in a set of
studies aimed at manipulating skeletal regeneration capacities. While both salamanders and lizards regenerate
their tails, salamanders regenerate near-perfect copies of original tails, while regenerated lizard tails are known
as an “imperfect replicates” with several key anatomical differences compared to originals. The most striking of
these “imperfections” concerns the lack of dorsoventral patterning and segmentation in regenerated lizard tail
skeletons. Progress made under our original proposal identified the signals regulating regenerated skeletal tissue
induction and patterning, creating the first dorsoventrally-patterned regenerated lizard tails. This renewal
proposal focuses on later stages of skeletal maturation that, given the proper signals, culminate in segmentation.
Our recent comparative analyses indicate that regenerated skeleton segmentation is dependent upon three
distinct milestones: (1) perichondrium patterning, (2) cartilage hypertrophy, and (3) periosteum formation. Both
salamander and lizard regenerated tail skeletons begin as unsegmented cartilage elements. Our preliminary
findings suggest a novel role for spinal cord meningeal tissues in regulating skeleton segmentation. Regenerated
salamander, but not lizard, meninges contain specialized cell populations capable of recreating embryonic
segmentation signals in adjacent perichondrium and initiating a signaling cascade that transforms the entire
regenerated skeleton. Some of these signals induce cartilage hypertrophy in salamander cartilage before anti-
ossification processes that dominate lizard skeletons have the chance to stagnate cartilage maturation. Other
signals missing in lizard tails allow salamander bone cells to survive and promote periosteum development.
Based on this comparative analysis, we hypothesize the feasibility of mechanistically based interventions to shift
the “imperfectly” regenerating lizard tail to phenocopy the “perfectly” regenerating salamander tail. The Aims are:
(1) Introduce patterning to regenerated lizard tail perichondrium by supplementing adult spinal cord meninges
with embryonic segmenting cells; (2) Induce regenerated lizard cartilage hypertrophy by interrupting anti-
maturation signals that result in dysregulated cartilage development; and (3) Promote periosteum formation
within regenerated lizard tails by inducing bone cell survival and recruitment. An integrated approach is
proposed, incorporating a unique, asexually reproducing lizard species with in vivo surgical manipulations to
deliver cells and bioactive agents toward manipulating skeletal development. We believe that this approach will
produce the first regenera...

## Key facts

- **NIH application ID:** 10756080
- **Project number:** 5R01GM115444-08
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Thomas Peter Lozito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $346,500
- **Award type:** 5
- **Project period:** 2016-05-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756080

## Citation

> US National Institutes of Health, RePORTER application 10756080, Why don’t lizards regenerate perfect tails like salamanders? (5R01GM115444-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10756080. Licensed CC0.

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