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Characterization of NF-kappa B/I kappa B proteins in zebra fish and their involvement in notochord development.

Abstract：

:Although largely involved in innate and adaptive immunity, NF-kappa B plays an important role in vertebrate development. In chicks, the inactivation of the NF-kappa B pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-kappa B activity leads to prenatal death and neural tube defects. Here, we report the cloning and characterization of NF-kappa B/I kappa B proteins in zebra fish. Despite being ubiquitously expressed among the embryonic tissues, NF-kappa B/I kappa B members present distinct patterns of gene expression during the early zebra fish development. Biochemical assays indicate that zebra fish NF-kappa B proteins are able to bind consensus DNA-binding (kappa B) sites and inhibitory I kappa B alpha proteins from mammals. We show that zebra fish I kappa B alphas are degraded in a time-dependent manner after induction of transduced murine embryo fibroblasts (MEFs) and that these proteins are able to rescue NF-kappa B activity in I kappa B alpha(-/-) MEFs. Expression of a dominant-negative form of the murine I kappa B alpha (mI kappa B alpha M), which is able to block NF-kappa B in zebra fish cells, interferes with the notochord differentiation, generating no tail (ntl)-like embryos. This phenotype can be rescued by coinjection of the T-box gene ntl (Brachyury homologue), which is typically required for the formation of posterior mesoderm and axial development, suggesting that ntl lies downstream of NF-kappa B . We further show that ntl and Brachyury promoter regions contain functional kappa B sites and NF-kappa B can directly modulate ntl expression. Our study illustrates the conservation and compatibility of NF-kappa B/I kappa B proteins among vertebrates and the importance of NF-kappa B pathway in mesoderm formation during early embryogenesis.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Correa RG,Tergaonkar V,Ng JK,Dubova I,Izpisua-Belmonte JC,Verma IM

doi

10.1128/MCB.24.12.5257-5268.2004

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

5257-68

issue

eissn

0270-7306

issn

1098-5549

pii

24/12/5257

journal_volume

pub_type

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Characterization of NF-kappa B/I kappa B proteins in zebra fish and their involvement in notochord development.