Shox2 regulates osteogenic differentiation and pattern formation during hard palate development in mice

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Mammalian palatogenesis involves cranial neural crest cells forming the hard palate.
• The hard palate consists of the palatine process of the maxilla and the palatine.
• The cellular origins and molecular patterning of these structures are not fully understood.

Purpose of the Study:

• To investigate the role of Short stature homeobox 2 (Shox2) in hard palate development.
• To determine if the palatine process of the maxilla and palatine originate from the same cell lineage.
• To elucidate the molecular mechanisms underlying hard palate patterning.

Main Methods:

• Utilized mouse models with Shox2 deficiency and overexpression.
• Performed RNA sequencing and assay for transposase-accessible chromatin sequencing (ATAC-seq).
• Conducted H3K27ac ChIP-Seq and transient transgenic enhancer assays.

Main Results:

• Shox2 deficiency specifically impaired the palatine process of the maxilla, not the palatine.
• Shox2 overexpression led to a hyperplastic palatine process of the maxilla and hypoplastic palatine.
• Shox2 regulates skeletogenic gene expression via accessible chromatin in the anterior palate.
• Shox2 interacts with distal cis-regulatory elements in an anterior palate-specific manner.

Conclusions:

• The palatine process of the maxilla and palatine likely arise from distinct cell lineages with different ossification mechanisms.
• Shox2 plays a lineage-autonomous role in patterning and osteogenesis of the anterior hard palate.
• Shox2 acts through distal cis-regulatory elements to control skeletogenic gene expression and hard palate patterning.