# Cfp1 Action in Cartilage Development

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $430,867

## Abstract

Endochondral ossification is a process by which mesenchymal progenitor cells (MPCs) differentiate into
cartilage prior to forming bone. Perturbations in their capacity to differentiate leads to skeletal anomalies.
Therefore, deciphering the molecular mechanisms controlling these cells is crucial for both understanding the
causes of skeletal diseases as well as developing new therapeutic approaches to restore the skeleton. While
transcription factors and signaling molecules have been linked to cartilage development, less is known about
the upstream mechanisms that initiate the process. Recent data from mice and humans implicate epigenetic
regulatory factors as critical modulators of MPC function. CXXC finger protein 1 (Cfp1) is an epigenetic
regulatory factor implicated in progenitor cell function, though the mechanism(s) of its action have not been
well defined. To address this, we deleted Cfp1 specifically from limb bud mesenchyme. Preliminary data show
that loss of Cfp1 results in the complete absence of forelimbs at birth. Subsequent analysis of embryonic
forelimbs revealed that, in the absence of Cfp1, MPCs failed to undergo condensation, the initial step in
chondrogenesis. Whole transcriptome analysis revealed a dramatic reduction in chondrogenic gene markers,
including the master transcriptional regulator, Sox9, which is required for condensation, further implicating Cfp1
as a crucial factor in the early stages of cartilage formation. Preliminary data indicate that Cfp1 may regulate
this key developmental step through activation of BMP signaling. Further, while mutant hindlimbs form they are
severely stunted, consistent with our observation that deletion of Cfp1 in chondrocytes results in shorter bones.
Together, these data suggest that Cfp1 also regulates chondrocyte differentiation and maturation during
growth plate development. We hypothesize that Cfp1 regulates multiple stages of cartilage development
through modulation of essential transcriptional regulators and key signaling pathways. Further study of Cfp1
will provide fundamental insight into how epigenetic regulation of cellular and molecular mechanisms impacts
chondrogenesis and growth plate development. We propose: 1) to identify Cfp1's actions during chondrocyte
differentiation in the developing long bone, 2) to determine the effect of Cfp1 loss on growth plate development
and 3) to identify the Cfp1 regulatory network during cartilage development.

## Key facts

- **NIH application ID:** 10116284
- **Project number:** 5R01AR074982-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Diana Lynn Carlone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,867
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116284

## Citation

> US National Institutes of Health, RePORTER application 10116284, Cfp1 Action in Cartilage Development (5R01AR074982-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116284. Licensed CC0.

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