# Sonic hedgehog signaling and skeletal patterning during zebrafish fin regeneration

> **NIH NIH F31** · UNIVERSITY OF OREGON · 2024 · $48,974

## Abstract

PROJECT SUMMARY
This project provides the applicant with Ph.D. training in cell and developmental biology. Thesis research will
further our understanding how cell signaling mediates cell-cell interactions to facilitate intricate skeletal patterning.
Additionally, the applicant will pursue activities supporting professional development, advanced imaging,
mentorship, and science communication skills. Zebrafish rapidly and robustly regenerate their caudal fins,
including their characteristic bony ray skeleton. During fin development and regeneration, most rays branch to
form distinct daughter rays. Ray branching occurs through the splitting of progenitor osteoblast (pOb) pools
adjacent to sonic hedgehog a (shha)-expressing basal epidermal cells (bEps). The shha-expressing bEp
domains themselves split prior to overt branching. Small molecule inhibition of Sonic hedgehog/Smoothened
(Shh/Smo) signaling specifically prevents ray branching. The unbranched rays grow to their normal length and
the shha-expressing bEp domains still split. However, the Shh/Smo target genes and how they influence cell
behaviors that divide pOb pools are unknown. This proposal aims to identify relevant Shh/Smo target genes and
how they promote interactions between shha-expressing bEps and pObs for ray branching morphogenesis.
Previous studies and the applicant’s preliminary data using a new long-term live imaging approach indicate that
collectively migrating shha-expressing bEps contact individual pObs and progressively escort them into split
pools during ray outgrowth. Further, the applicant has identified a Shh-dependent gene, fibrillin 2b (fbn2b), that
when germline mutated causes unbranched rays in regenerated fins. Together, these results support the
applicant’s hypothesis that Shh/Smo promotes transient Fbn2b-dependent heterotypic cell associations
underlying co-movements of shha-expressing bEps and pObs. The applicant will explore this hypothesis with
two aims. Aim 1 will identify Shh/Smo target genes that mediate ray branching during fin regeneration. Aim 2 will
define Shh/Smo driven associations of migrating Shh+ basal epidermal cells and underlying progenitor
osteoblasts throughout the duration of branching morphogenesis. Completing these aims will reveal Shh/Smo-
dependent, coordinated cell behaviors and new mediators of skeletal ray branching morphogenesis. These
insights will advance our mechanistic understanding of skeletal outgrowth and patterning with potential
biomedical significance for skeletal regenerative medicine.

## Key facts

- **NIH application ID:** 10903645
- **Project number:** 1F31HD113401-01A1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Samuel G Horst
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-06-16 → 2027-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903645

## Citation

> US National Institutes of Health, RePORTER application 10903645, Sonic hedgehog signaling and skeletal patterning during zebrafish fin regeneration (1F31HD113401-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10903645. Licensed CC0.

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