# microRNA tuning of neural crest osteogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $383,281

## Abstract

PROJECT SUMMARY
Every 4 ½ minutes, a baby is born with a birth defect, including such that affect the craniofacial skeleton.
These facial malformations cause disfigurement leading to long-term psychological impact and are often
associated with physical dysfunction imposing tremendous burden on the affected individuals and their
families. Although the causes for most of these severe developmental pathologies are still unknown, it is clear
that the inappropriate formation and differentiation of neural crest (NC) cells, the cells that normally give rise to
the osteoblasts in the affected craniofacial skeleton, plays a large part. Given the causality between
miscontrolled osteoblast differentiation from the NC and the tissue malformations arising from it, an
understanding of the molecular networks underlying NC development is crucial for the potential treatment or
prevention of craniofacial defects, yet far from complete. For instance, the contribution of epigenetic regulators,
such as microRNAs (miRNAs), to the formation of the craniofacial bones remains understudied, despite their
potential as diagnostic markers.
We study here the epigenetic regulation of NC development by a specific miRNA, miR361, which we have
previously identified in our lab as being pro-osteogenic in an in vitro model of NC-osteogenesis. Characterizing
the miR361 expression domain in mouse and Xenopus embryos coupled with the assessment of skeletal and
NC phenotypes when miR361 is knocked out or overexpressed in these organisms will validate the function of
miR361 during NC development in vivo. Assessing miR361's contribution to NC development using an
innovative and effective in vitro NC differentiation model based on human pluripotent stem cells will show
relevance for this microRNA in human development. Elaborating on the direct miR361 mRNA target and
identifying NC-specific loci that are transcriptionally regulated downstream of miR361 will define the
relationship between this miRNA, transcriptional activation in NC cells and their subsequent propensity for
osteoblast differentiation. This knowledge is highly impactful as there is currently no information in the public
domain that could explain the role of miR361 in bone development from the NC nor in any aspect of
differentiation, development or disease. The results gained from this study will aid in the development of a
more complete understanding of craniofacial osteogenesis that is inclusive of epigenetic regulators and
promises to illuminate causes and treatments of developmental disorders of the craniofacial region in humans,
which has a high priority in NIDCR's long-range plan.

## Key facts

- **NIH application ID:** 9982300
- **Project number:** 5R01DE025330-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Nicole Isolde zur Nieden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,281
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982300

## Citation

> US National Institutes of Health, RePORTER application 9982300, microRNA tuning of neural crest osteogenesis (5R01DE025330-05). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9982300. Licensed CC0.

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