In the developing limb, the Sonic hedgehog (Shh) signaling protein works through the Gli family of transcription factors to control tissue growth and patterning.
To discover downstream targets of Shh/Gli signaling, Chin Chiang, Ph.D., professor of Cell and Developmental Biology, and colleagues analyzed the collection of genes that are “turned on” in the early limb bud.
They identified Has2, which encodes an enzyme that synthesizes the extracellular matrix component hyaluronan, as a Gli target. They showed that Shh signaling directly regulates Has2 expression during early limb development. Mice with conditional Has2 mutations in the developing limb had patterning and joint defects and impaired cartilage development.
The study, reported in the March 15 Developmental Biology, identifies Has2 as a novel downstream target of Shh signaling and points to a role for Shh in regulating the composition of the extracellular matrix scaffold in the developing limb. The findings may have relevance for other developmental, injury or disease contexts where Shh signaling is activated, such as in certain types of tumors.
This research was supported by a grant from the National Institutes of Health (HD049667).
