Kim, G.Y., Kim, H.Y., Kim, H.T., Moon, J.M., Kim, C.H., Kang, S., and Rhim, H. (2012) HtrA1 Is a Novel Antagonist Controlling Fibroblast Growth Factor (FGF) Signaling via Cleavage of FGF8. Molecular and cellular biology. 32(21):4482-4492.
Accumulating evidence suggests that High temperature requirement A1 (HtrA1) is involved in modulating crucial cellular processes
and implicated in life-threatening diseases, such as cancer and neuropathological disorders; however, the exact functions
of this protease in vivo remain unknown. Here, we show that loss of HtrA1 function increases Fibroblast growth factor (FGF) 8 mRNA levels and triggers activation of FGF signaling, resulting in dorsalization in zebrafish embryos. Notably, HtrA1 directly
cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling that is essential
for many physiological processes. Therefore, HtrA1 is indispensable for dorsoventral patterning in early zebrafish embryogenesis
and serves as a key upstream regulator of FGF signaling through the control of FGF levels. Furthermore, this study offers
insight into new strategies to control human diseases associated with HtrA1 and FGF signaling.