Single-cell analysis identifies a key role for Hhip in murine coronal suture development

Nat Commun. 2021 Dec 8;12(1):7132. doi: 10.1038/s41467-021-27402-5.


Craniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip-/- coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Development
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Proliferation
  • Cranial Sutures / growth & development*
  • Cranial Sutures / pathology
  • Craniosynostoses
  • DNA Topoisomerases, Type II
  • Female
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / metabolism*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mesoderm
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis / genetics
  • Osteogenesis / physiology
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins
  • Sequence Analysis, RNA
  • Signal Transduction
  • Single-Cell Analysis / methods*
  • Skull
  • Transcriptome


  • Carrier Proteins
  • Hedgehog Proteins
  • Hhip protein, mouse
  • Membrane Glycoproteins
  • Poly-ADP-Ribose Binding Proteins
  • DNA Topoisomerases, Type II
  • Top2a protein, mouse