Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development

Dev Biol. 2015 Apr 15;400(2):180-90. doi: 10.1016/j.ydbio.2015.02.010. Epub 2015 Feb 23.

Abstract

Growth factor signaling regulates tissue-tissue interactions to control organogenesis and tissue homeostasis. Specifically, transforming growth factor beta (TGFβ) signaling plays a crucial role in the development of cranial neural crest (CNC) cell-derived bone, and loss of Tgfbr2 in CNC cells results in craniofacial skeletal malformations. Our recent studies indicate that non-canonical TGFβ signaling is activated whereas canonical TGFβ signaling is compromised in the absence of Tgfbr2 (in Tgfbr2(fl/fl);Wnt1-Cre mice). A haploinsufficiency of Tgfbr1 (aka Alk5) (Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)) largely rescues craniofacial deformities in Tgfbr2 mutant mice by reducing ectopic non-canonical TGFβ signaling. However, the relative involvement of canonical and non-canonical TGFβ signaling in regulating specific craniofacial bone formation remains unclear. We compared the size and volume of CNC-derived craniofacial bones (frontal bone, premaxilla, maxilla, palatine bone, and mandible) from E18.5 control, Tgfbr2(fl/fl);Wnt1-Cre, and Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)mice. By analyzing three dimensional (3D) micro-computed tomography (microCT) images, we found that different craniofacial bones were restored to different degrees in Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+) mice. Our study provides comprehensive information on anatomical landmarks and the size and volume of each craniofacial bone, as well as insights into the extent that canonical and non-canonical TGFβ signaling cascades contribute to the formation of each CNC-derived bone. Our data will serve as an important resource for developmental biologists who are interested in craniofacial morphogenesis.

Keywords: Craniofacial bone development; Micro-computed tomography; Mouse embryo; TGFβ signaling.

Publication types

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

MeSH terms

  • Animals
  • Bone Development*
  • Facial Bones / anatomy & histology
  • Facial Bones / embryology*
  • Imaging, Three-Dimensional
  • Mice
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Skull / embryology*
  • Transforming Growth Factor beta / metabolism
  • X-Ray Microtomography

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II