Research Summary

Exovesicular Hedgehog signaling during tissue patterning and cancer progression

Patterning of developing embryos requires signaling via different molecules in spacio- temporally regulated manner. Hedgehog is one such highly conserved signaling protein required for embryonic patterning and is also hyper-activated in several cancers. Hedgehog molecules are known to be anchored to cell membrane via their peculiar lipid modifications (Cholesterol & Palmitate). Hence mechanism of Hedgehog release, transport and reception, has intrigued several researchers in the field which involves intricate processes at molecular and cellular levels. Several evidences including our previous work suggest that Hedgehog proteins are secreted on exovesicles. We find that Hedgehog proteins are secreted on atleast two types of exovesicles with distinct proteins and miRNAs. Apart from exovesicles, there are other reported extracellular forms of Hedgehog proteins. Currently, the need for secretion of Hedgehog in different extracellular forms remains unclear. Our group is interested specifically in probing the biogenesis of different types of exovesicles ferrying vertebrate Hedgehog (i.e. Shh) and mechanism of miRNA packaging within them. We are also seeking clarity on the physiological implications of Shh-exovesicle associated partners (proteins & miRNAs) on its function during tissue patterning as well as in diseases such as cancer.