Title:C-Jun Terminal Kinases Play an Important Role in Regulating Embryonic Survival and Eye Development in Vertebrates
Volume: 13
Issue: 1
Author(s): L. Liu, D. W.-C. Li, S.-J. Liu, Y.-Z. Liu, M.-B. Yu, L.-X. Luo, X.-L. Liu, M.-X. Wu, K.-L. Wu, L. Li, X.-Q. Huang, W.-J. Han, L. Chen, Y. Liu, F.-Y. Liu, X.-C. Tang, X. Li, X.-W. Chen, Z.-L. Li and Z.-X. Huang
Affiliation:
Keywords:
JNK1, JNK2, JNK3, development, cell differentiation, retina, lens, cataract
Abstract: The c-Jun N-terminal kinases (JNKs) constitute one of the three major types of mitogen-activated
protein kinases. Previous studies showed that JNK mediates multiple signaling transduction pathways
implicated in cell proliferation, differentiation, inflammation, stress response and apoptosis in mammals. In the
present study, we use goldfish as a model system and demonstrate that JNK kinases are necessary to
promote embryonic survival and regulate eye development in vertebrates. During goldfish development, JNK1
and JNK2 are expressed at every stage from cleavage to hatching larvae. JNK3 is turned on at the gastrulation
stage and then expressed at similar level to that of JNK2. JNK1 activity remains slightly fluctuated during
different developmental stages. Inhibition of JNK activity caused massive apoptosis of blastula cells and
significant death of goldfish embryos, which are associated with altered expression of the anti-apoptotic
regulator, Mcl-1 and the proapoptotic regulator, Bak. These results provide novel information regarding the
mechanisms by which JNKs promote embryonic survival. In addition, the embryos that survived inhibition of
JNK activity displayed severe phenotype in the eye with clear microphthalmia and lens coloboma. To confirm
that the observed phenotype is derived from JNK activity deficiency, we expressed JNK dominant negative
mutant (DNM-JNK) in goldfish. Expression of DNM-JNK also caused similar phenotypes with altered
expression of pax-6, Sox-2 and β-crystallin. Together, our results demonstrate that JNKs play important roles
in promoting survival of vertebrate embryos and regulating development of vertebrate eye.
