PUBLICATION

HtrA1 Is a Novel Antagonist Controlling Fibroblast Growth Factor (FGF) Signaling via Cleavage of FGF8

Authors
Kim, G.Y., Kim, H.Y., Kim, H.T., Moon, J.M., Kim, C.H., Kang, S., and Rhim, H.
ID
ZDB-PUB-120907-8
Date
2012
Source
Molecular and cellular biology   32(21): 4482-4492 (Journal)
Registered Authors
Kim, Cheol-Hee, Kim, Hyun-Taek
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Fibroblast Growth Factor 8/genetics
  • Fibroblast Growth Factor 8/metabolism*
  • Gene Expression Regulation, Developmental
  • Morpholinos/genetics
  • Phenotype
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Serine Endopeptidases/deficiency
  • Serine Endopeptidases/metabolism*
  • Signal Transduction/genetics
  • Zebrafish/embryology
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22949504 Full text @ Mol. Cell. Biol.
Abstract

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.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes