04-P002 Axis determination in the early chick embryo

Noggin1 is a famous embryonic neural inducer that can sequester TGF-beta cytokines of Bone Morphogenetic Protein family, thereby antagonizing Smad1-dependent signaling pathway activity. During early embryogenesis noggin1 executes two major biological functions: conversion of embryonic mesoderm into skeletal muscles (dorsalization) and of ectoderm into neural tissue (neuralization). Anterior neural tissue is involved in the formation of head structures and particularly in the development of rostral forebrain (RF), which is important evolutionary innovation of Vertebrates responsible for their higher cognitive functions. Besides ‘‘classical” noggin1, two other groups of noggin proteins, noggin2 and noggin4, were recently identified in Vertebrates. Different expression patterns of noggin1, noggin2 and noggin4 in early embryonic development and their amino acid sequence distinctions suggest that these factors may execute different biological functions. Noggin2 is specifically expressed in Xenopus embryos in the RF primordium where it presumably duplicates antagonizing effect of noggin1 on BMP signaling. Now we report that in addition to latter function, and in contrast to noggin1, noggin2 can also antagonize another TGF-beta factor, activin, which, in its turn, influences on the activity of Smad2-dependent signaling pathway. Down-regulation of noggin2 causes severe abnormalities of forehead development, indicating its crucial role in this process. In case of ectopical expression of noggin2, its ability to inhibit both BMP and activin signaling pathways can result in development of secondary forehead structures. Consistently, we show that inhibition of activin signaling by noggin2 in cells of the anterior neural plate is essential for the forebrain development in normal embryogenesis.