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XB-ART-52888
Development January 1, 2017; 144 (2): 321-333.

An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation.

Rothe M , Kanwal N , Dietmann P , Seigfried FA , Hempel A , Schütz D , Reim D , Engels R , Linnemann A , Schmeisser MJ , Bockmann J , Kühl M , Boeckers TM , Kühl SJ .


Abstract
The signal-induced proliferation-associated family of proteins comprises four members, SIPA1 and SIPA1L1-3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts upstream of Sipa1l3 during eye development, with both Sipa1l3 and Epha4 required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax We demonstrate that canonical Wnt signaling is inhibited downstream of Epha4 and Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an upregulation of axin2 expression, a direct Wnt/β-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/β-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells, resulting in congenital cataracts.

PubMed ID: 27993984
Article link: Development

Genes referenced: acss2.2 arr3 arrb2 axin2 capza1 celf1 cryaa cryba1 dvl1 dvl2 epha4 myc pax6 pes1 pou4f1 rax rho rpe sipa1 sipa1l1 sipa1l2 sipa1l3 sox3 vsx1 wnt1
GO keywords: embryonic camera-type eye development
Antibodies: Epha4 Ab1 Myc Ab1 Sipa1l3 Ab1 Tubulin I+II Ab1
Morpholinos: epha4 MO1 sipa1l3 MO1

Disease Ontology terms: cataract 45
OMIMs: CATARACT 45; CTRCT45

Article Images: [+] show captions


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