Title

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

UMMS Affiliation

Howard Hughes Medical Institute and Program in Molecular Medicine

Publication Date

5-21-2003

Document Type

Article

Subjects

Animals; Bone Morphogenetic Proteins; Coloboma; Cytokines; DNA-Binding Proteins; Drosophila; Hedgehog Proteins; JNK Mitogen-Activated Protein Kinases; Lens, Crystalline; Mice; Mitogen-Activated Protein Kinases; PAX2 Transcription Factor; Signal Transduction; Trans-Activators; Transcription Factors

Disciplines

Life Sciences | Medicine and Health Sciences

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).

Rights and Permissions

Citation: Genes Dev. 2003 May 15;17(10):1271-80. Link to article on publisher's site

DOI of Published Version

10.1101/gad.1087303

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Genes and development

PubMed ID

12756228