How Skeletal Stem Cells form the Blueprint of the Face

A new study from the laboratory of University of Southern California (USC) Stem Cell researcher J Gage Crump, who is at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, has identified the key molecular signals that control the critical timing of the development of the vertebrate face.

Previous work has demonstrated that two molecular signals, in particular the JaggedNotch and Endothelin 1 signaling, are integral for shaping the face. Loss of either of these signals results in facial deformities in zebrafish and humans. This illustrates the essential contribution these signaling pathways make to the development of the face.

Lindsey Barske, a researcher in Crump’s laboratory and her colleagues utilized sophisticated genetic, genomic, and imaging tools to study face formation in zebrafish and showed that the Jagged-Notch and Endothelin 1 pathways work in tandem to control when and where the facial stem cells form face-specific cartilage.

In the lower part of the face, the Endothelin 1 signal accelerates cartilage formation early in development, but in the upper face, the Jagged-Notch signal transduction pathway produces signals that prevent stem cells from making cartilage until later in development.

Barske and her colleagues discovered that these timing differences in facial stem cell activity and facial cartilage production play a major role in making the upper and lower cartilage regions of the face.

The earliest blueprint of the facial skeleton is established by intersecting signals that control when stem cells transform cartilage into bone. It also appears that small tweaks to the timing of these events accounts for the different skull shapes observed in vertebrate animals. Also, small, nuanced changes in facial cartilage production and ossification can also account for the diverse array of facial shapes observed in humans.

This work was published in PLOS Genetics 12(4): e1005967. doi:10.1371/journal.pgen.1005967.