Neugebauer, J.M., Cadwallader, A.B., Amack, J.D., Bisgrove, B.W., and Yost, H.J. (2013) Differential roles for 3-OSTs in the regulation of cilia length and motility. Development (Cambridge, England). 140(18):3892-3902.
As cells integrate molecular signals from their environment, cell surface receptors require modified proteoglycans for the
robust activation of signaling pathways. Heparan sulfate proteoglycans (HSPGs) have long unbranched chains of repetitive disaccharide
units that can be sulfated at specific positions by heparan sulfate O-sulfotransferase (OST) families. Here, we show that
two members of the 3-OST family are required in distinct signaling pathways to control left-right (LR) patterning through
control of Kupffer’s vesicle (KV) cilia length and motility. 3-OST-5 functions in the fibroblast growth factor pathway to
control cilia length via the ciliogenic transcription factors FoxJ1a and Rfx2. By contrast, a second 3-OST family member,
3-OST-6, does not regulate cilia length, but regulates cilia motility via kinesin motor molecule (Kif3b) expression and cilia
arm dynein assembly. Thus, two 3-OST family members cell-autonomously control LR patterning through distinct pathways that
regulate KV fluid flow. We propose that individual 3-OST isozymes create distinct modified domains or ‘glycocodes’ on cell
surface proteoglycans, which in turn regulate the response to diverse cell signaling pathways.