# Composite tissue patterning in mammalian digit tip regeneration

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $771,691

## Abstract

PROJECT SUMMARY
The digit tips of many mammals, including humans, innately regenerate following amputation. Multi-tissue digit
tip regeneration requires coordinated proliferation and interaction of many cell types in a structure termed the
‘blastema’. Significant progress has been made in defining the origin and cellular composition of the mouse
digit tip blastema, but there is a gap in our understanding of how the heterogeneous blastema becomes a
correctly organized and shaped composite tissue. This proposal focuses on defining the molecular
mechanism(s) of patterning the regenerating mouse digit tip. In general, broad similarities between the
regenerative blastema and the embryonic limb bud underlie the hypothesis that gene networks required for
embryonic limb patterning are re-deployed in the regenerative blastema. While studies support this hypothesis
in some non-mammalian models of limb regeneration, our data demonstrate that this is not true for dorsal-
ventral patterning during mouse digit tip regeneration. This suggests that mammalian and non-mammalian
limb-derived blastemas may employ different mechanisms for re-establishing limb tissue morphology. We
propose that the mammalian digit tip blastema utilizes non-developmental patterning mechanisms and
receives molecular patterning cues from the nail epithelium. In this proposal, we focus on the dorsal-ventral
and proximal-distal anatomical axes; we aim to determine the patterning mechanism(s) in the mouse digit tip
blastema and to determine how manipulation of these pathways during regeneration impacts morphology.
Toward this, we will model and molecularly define proximal-distal patterning genes using computational and
genetic approaches. We will also use grafting studies to determine the tissue patterning autonomy of the digit
tip blastema. Finally, we will visualize putative dorsal-ventral electrochemical gradients in the blastema and
perform gain and loss of function studies to manipulate these signals. Collectively, the data generated from this
project will reveal patterning mechanisms for mammalian digit tip regeneration and highlight how this may be
fundamentally different from non-mammalian limb regeneration models. This research will ultimately inform
blastema induction efforts for mammalian full limb amputations because exogenous patterning information may
need to be provided.

## Key facts

- **NIH application ID:** 10893682
- **Project number:** 1R01HD115260-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jessica A Lehoczky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $771,691
- **Award type:** 1
- **Project period:** 2024-04-02 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893682

## Citation

> US National Institutes of Health, RePORTER application 10893682, Composite tissue patterning in mammalian digit tip regeneration (1R01HD115260-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10893682. Licensed CC0.

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