# Ribosomal RNA transcription is spatiotemporally regulated and functionally required during neural crest,bone and cartilage development

> **NIH NIH F31** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $30,320

## Abstract

Project Summary
 Understanding the mechanisms that govern craniofacial development is very important given
that craniofacial malformations account for approximately one third of congenital anomalies.
Craniofacial anomalies occur frequently in tissue-specific disorders termed Ribosomopathies.
Ribosomopathies result from perturbations in ribosome biogenesis which is a global mechanism
required for cell growth, proliferation and survival. One craniofacial birth defect that is also a
ribosomopathy is Treacher Collins Syndrome (TCS) which occurs in 1 in 50,000 live births and is
characterized by disruptions in the development of neural crest cell (NCC), a population of cells that
give rise to most of the craniofacial bone and cartilage. Mutations in TCOF1, POLR1C and POLR1D
cause TCS. TCOF1 associates with RNA Polymerase I (Pol I), which transcribes ribosomal RNA
(rRNA), a rate-limiting step of ribosome biogenesis. POLR1C and POLR1D are subunits of Pol I and
III. Given the global nature and importance of Pol I and III transcription, it is remarkable that
perturbation of rRNA transcription results in tissue-specific defects. Therefore, I hypothesize that the
tissue-specific defects characteristic of Treacher Collins Syndrome and other ribosomopathies occur
due to the dynamic spatiotemporal regulation of Pol I and III subunit activity and rRNA transcription,
and spatiotemporal tissue-specific threshold requirements for ribosome biogenesis. More specifically,
I propose that NCC require high levels of rRNA transcription and are thus very susceptible to
disruptions in rRNA transcription and ribosome biogenesis.
 This study will address the specific spatiotemporal roles and requirements of Pol I and III
subunits and rRNA transcription during embryogenesis. The goal of aim 1 is to investigate the
intrinsic requirements for Polr1c in NCC development and its overall function in craniofacial bone and
cartilage formation. The purpose of aim 2 is to determine if there is a tissue-specific requirement for
rRNA transcription and thus a tissue-specific sensitivity to disruptions in ribosome biogenesis.

## Key facts

- **NIH application ID:** 9837431
- **Project number:** 5F31DE027860-03
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Karla Yadira Terrazas-Falcon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,320
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837431

## Citation

> US National Institutes of Health, RePORTER application 9837431, Ribosomal RNA transcription is spatiotemporally regulated and functionally required during neural crest,bone and cartilage development (5F31DE027860-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9837431. Licensed CC0.

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