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

被引:79
作者
Weston, CR
Wong, A
Hall, JP
Goad, MEP
Flavell, RA
Davis, RJ [1 ]
机构
[1] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA
[2] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[3] Wyeth Ayerst Res, Investigat Pathol, Andover, MA 01810 USA
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA
关键词
MAP kinase; JNK; bone morphogenetic protein-4; sonic hedgehog; Pax2; coloboma;
D O I
10.1101/gad.1087303
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Ink family (Jnk1, Jnk2, and Jnk3) are viable and survive without overt structural abnormalities. Here we show that mice with a compound deficiency in Ink expression can survive to birth, but fail to close the optic fissure (retinal coloboma). We demonstrate that INK 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 INK to regulate BMP4 expression during optic fissure closure is conserved in Drosophila during dorsal closure, a related morphogenetic process that requires INK-regulated expression of the BMP4 ortholog Decapentaplegic (Dpp).
引用
收藏
页码:1271 / 1280
页数:10
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