Work

JNK initiates a cytokine cascade that causes Pax2 expression and closure of the optic fissure

Year: 2003

Type: preprint

Abstract: The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases is stimulated in response to a wide array of cellular stresses and proinflammatory cytokines. Mice lacking individual members of the Jnk family (Jnk1, Jnk2, and Jnk3) are viable and survive without overt structural abnormalities. Here we show that mice with a compound deficiency in Jnk expression can survive to birth, but fail to close the optic fissure (retinal coloboma). We demonstrate that JNK initiates a cytokine cascade of bone morphogenetic protein-4 (BMP4) and sonic hedgehog (Shh) that induces the expression of the paired-like homeobox transcription factor Pax2 and closure of the optic fissure. Interestingly, the role of JNK to regulate BMP4 expression during optic fissure closure is conserved in Drosophila during dorsal closure, a related morphogenetic process that requires JNK-regulated expression of the BMP4 ortholog Decapentaplegic (Dpp).

Source: Genes & Development

DOI: 10.1101/gad.1087303

Authors: Claire R. Weston, Anthony Wong, J. Perry Hall, Mary E.P. Goad, Richard A. Flavell, Roger J. Davis

Institutions: Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Yale University, Wyeth

Language: English

Topic: Ocular Disorders and Treatments

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Howard Hughes Medical Institute, National Cancer Institute