JNK initiates a cytokine cascade that causes Pax2 expression and closure of the optic fissure
- Claire R. Weston1,
- Anthony Wong2,
- J. Perry Hall1,4,
- Mary E.P. Goad2,
- Richard A. Flavell3, and
- Roger J. Davis1,5
- 1Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; 2Investigative Pathology, Wyeth Research, Andover, Massachusetts 01810, USA; 3Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
Abstract
The c-Jun NH2-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).
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Footnotes
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Present address: 4Wyeth Research, Cambridge, MA 02140, USA.
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↵5 Corresponding author.
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E-MAIL Roger.Davis{at}umassmed.edu; FAX (508) 856-3210.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1087303.
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- Received February 21, 2003.
- Accepted March 28, 2003.
- Cold Spring Harbor Laboratory Press
