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


Document Type



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


Life Sciences | Medicine and Health Sciences


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).

DOI of Published Version



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

Journal/Book/Conference Title

Genes and development

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Link to Article in PubMed

PubMed ID