# Mechanisms of cyclical degeneration and regeneration in an avian model system

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $233,500

## Abstract

RESEARCH STRATEGY
1. Summary of parent project
[From original submission of 1R35GM150562]
A central goal of regenerative medicine is to understand how cells functionally integrate into existing tissues to
restore homeostasis and behavior. Studies of regeneration following tissue damage in a group of ~6 species
have made considerable advances towards this goal by uncovering mechanisms that promote proliferation,
fate specification, and new cell survival. Pursuing these mechanisms, however, has revealed an underlying
problem: how tissue re-patterning is limited to provide functional restoration and the re-establishment of
homeostasis without detrimental overgrowth. To understand how growth and patterning are limited, and
conversely, how tissues regress controllably will require broadening the systems in which these phenomena
are examined to include models of natural, cyclical and highly stereotyped re-growth and degeneration. One
such system – seasonally breeding songbirds – offers an outstanding opportunity to test mechanistic hypoth-
eses of growth and degeneration and how events and outcomes at molecular and cellular levels impact higher-
level anatomy and behavior. This lab makes use of two different songbird species: Gambel’s white-crowned
sparrow (Zonotrichia leugophrys gambelli) and the domesticated canary (Serinus canaria domestica). White-
crowned sparrows are advantageous in having dramatic cycles of seasonal degeneration and regeneration of
the neural circuit that controls singing behavior; an extensive literature detailing their natural history; and high
tractability for experimental analyses due to their natural abundance and robustness in the lab. Canary breeds,
each having unique singing abilities and well-documented genetics, promise the ability to link historical
selection for particular allelic variants to regenerative form and function, and plasticity at the level of individuals
and populations. Exploiting the natural and dramatic degeneration–regeneration cycles in sparrows this
proposal aims to determine how cell death: (i) influences generation of new cells to limit total growth of neural
tissue and (ii) is finely tuned to prevent excessive degeneration of tissue and behavior while maintaining
competency for a return to homeostasis and subsequent plasticity. Exploiting the tight genetic control imposed
by breeders in selecting for exaggerated singing in canaries, the work aims to determine how diversification of
behavior arose from modifications to the balance between degeneration and regeneration, and how genetic
changes translate to cellular plasticity and emergence of novel behavior. Towards these goals, this program
will use a highly integrative and complementary set of approaches – including pharmacological manipulations
of intact neural circuits in freely behaving birds; classic cellular, molecular, and histological analyses; and state-
of-the-art genomic approaches – to interrogate the cellular, molecular, and evolution...

## Key facts

- **NIH application ID:** 11034730
- **Project number:** 3R35GM150562-01S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** TRACY ALISON LARSON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,500
- **Award type:** 3
- **Project period:** 2023-09-22 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11034730

## Citation

> US National Institutes of Health, RePORTER application 11034730, Mechanisms of cyclical degeneration and regeneration in an avian model system (3R35GM150562-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11034730. Licensed CC0.

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