Lineage tracing of cells expressing the ciliary gene IFT140 during bone development

Dev Dyn. 2021 Apr;250(4):574-583. doi: 10.1002/dvdy.266. Epub 2020 Dec 5.

Abstract

Background: Primary cilia influence cell function and tissue development. Ciliary signaling is mediated by two intraflagellar transport (IFT) protein complexes, IFT-A and IFT-B. The IFT-A complex is responsible for retrograde transport, and IFT140 is a core protein in the A complex. Mutations in IFT140 cause a variety of skeletal disorders. However, the expression and role of IFT140 during bone development remain unclear. In this study, to further explore the potential role of IFT140 in osteogenesis, we used cell lineage tracing and conditional knockout to analyze the distribution and function of IFT140-positive cells during bone formation.

Results: In newborn Ift140-creER; R26RtdTomato mice, IFT140-positive cells were mainly located in the medullary cavity and then migrated to and differentiated on the surface of trabecular and cortical bone. In contrast, the number of IFT140-positive cells significantly decreased in the adult stage, and these cells were only located in the bone marrow cavity for a short time. In Osx-cre; Ift140flox/flox mice, the loss of IFT140 in preosteoblasts caused bone loss in the trabecular bone area at 10 weeks.

Conclusion: The results revealed that IFT140-positive cells mainly contribute to the early stage of bone formation.

Keywords: bone development; cell lineage tracing; cilia; intraflagellar transport protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bone Diseases, Developmental / genetics
  • Carrier Proteins / physiology*
  • Cell Lineage
  • Mice
  • Mice, Knockout
  • Osteogenesis*

Substances

  • Carrier Proteins
  • IFT140 protein, mouse