# Molecular patterning of the hard palate during palatogenesis

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $321,694

## Abstract

Abstract/Summary
The mammalian palate is anatomically divided into the anterior bony hard palate and the posterior muscular
soft palate. However, how the anterior hard palate is patterned and how the palatal osteogenesis is controlled
remain unknown. It was recently demonstrated that in the developing branchial arches, the TALE superclass
homeodomain proteins particularly Meis proteins set up a ground state that is common to all the arches and
their derivatives whereas Hox transcription factors act as tissue-specific cofactor to specify the arch identity.
However, this raises a fundamental question as what factors interact with TALE factors to specify and
pattern the Hox-free first arch and its derivatives including the palate. The homeobox gene Shox2 is
expressed specifically in the anterior palatal mesenchyme, overlapping with the future bony hard palate
domain. We have shown previously that Shox2 mutation leads to not only a rare type anterior clefting of the
secondary palate, but also the significantly reduced bone formation in the hard palate, which, together with
-/-
the virtual loss of the stylopod in Shox2 limb, indicates an essential role for Shox2 in organ patterning and
skeletogenesis. Our preliminary studies present evidence that Shox2 mutation leads to premature/ectopic
 +
expression of Runx2 in Shox2-expressing palatal cells. RNA-Seq on Shox2 cells from E13 palatal shelves
and limbs demonstrates a genome-wide elevated expression of osteogenic genes in the absence of Shox2,
consistent with the observation that Shox2 overexpression in cranial neural crest lineage cells inhibits
osteogenesis. Moreover, Shox2 ChIP-Seq on the developing palate and limb reveals genome-wide
preferential occupation of Shox2 on the responsive cis-regulatory elements of genes bound by Hox and
TALE proteins, suggesting that in the Hox-free developing palate, Shox2 functions together with TALE
factors to pattern the hard palate and regulates osteogenesis. Based on the abovementioned observations, we
hypothesize that in the Hox-free palatal shelf, Shox2 interacts with TALE factors to establish the hard palate
identity by antagonizing Meis transcriptional output to prevent premature osteogenesis. In this application,
three specific aims are proposed to test this novel hypothesis rigorously: 1) to test the hypothesis that Shox2
expression prevents premature osteogenesis in the developing palate; 2) to test the hypothesis that Shox2
antagonizes the transcription output of Meis and to establish the functional mechanisms for Shox2; 3) to
determine the tissue specific chromatin landscape and identify specific enhancer elements underlying palate
formation. The results obtained will provide novel knowledge for understanding of palate development and
cleft palate formation, and provide solid foundation for future tissue engineering of palatal bone for clinical
treatment/repair of cleft palate defects.

## Key facts

- **NIH application ID:** 9852890
- **Project number:** 5R01DE026482-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Yiping Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,694
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852890

## Citation

> US National Institutes of Health, RePORTER application 9852890, Molecular patterning of the hard palate during palatogenesis (5R01DE026482-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852890. Licensed CC0.

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