# TGFbeta in the pathology and development of the spine

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $311,869

## Abstract

Project Summary.
The long-term objective of this study is to understand signals involved in development and maintenance of the
axial skeleton that can inform regenerative and engineering strategies. Members of the Tgfb superfamily are
secreted signaling proteins that regulate many aspects of skeletal biology. Polymorphisms and mutations in
genes that regulate Tgfb activity have been associated with pathology in the spine. It’s also been shown using
genetically engineered mice that Tgfbr2 is required for development and maintenance of the fibrous tissues in
the spine including the annulus fibrosus of the intervertebral disc, ligaments, and tendon. Previous results
obtained in my laboratory indicate that Tgfb regulates cell fate decisions in the sclerotome, the embryonic
progenitor of the connective tissues in the spine. In this application, we propose to address the instructive
mechanisms whereby Tgfb regulates embryonic formation of fibrous tissues in the spine. In addition, we
propose to address the problem of sclerotome resegmentation, an embryonic process that creates the spatial
organization of tissues in the spine. Alterations in resegmentation would be expected to alter the context in
which cells differentiate, affecting permissive signals and competence to respond to instructive signals that
govern cell fate decisions. Finally, using a mouse model developed in my laboratory, we will start to determine
the mechanisms of how Tgfb acts to maintain fibrous character in the postnatal annulus fibrosus. The overall
aims of this proposal are to: 1) Determine the signaling pathways used by Tgfb to generate fibrous tissues of
the spine during embryonic development; 2) To map the process of resegmentation and determine the
mechanism of Tgfb-mediated regulation and 3) To understand how Tgfb maintains annulus fibrosus
postnatally. The experiments described here will provide mechanistic information about development and
maintenance of the axial skeleton and provide a foundation for future regeneration and engineering strategies
in the spine.

## Key facts

- **NIH application ID:** 10881779
- **Project number:** 5R01AR078740-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Rosa A. Serra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,869
- **Award type:** 5
- **Project period:** 2023-07-04 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881779

## Citation

> US National Institutes of Health, RePORTER application 10881779, TGFbeta in the pathology and development of the spine (5R01AR078740-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881779. Licensed CC0.

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