04-P003 Induction of cranial placodes: The role of ectodermal competence

Abstract

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.In chick, although the polarity of the early embryo is specified by the time of egg-laying, the embryo is highly regulative: when a blastoderm-stage embryo (about 20,000 cells) is cut in half, both halves can develop an embryonic axis (Bertocchini et al., 2004; Lutz, 1949; Spratt and Haas, 1960). This implies that normal embryos possess inhibitory mechanisms that prevent formation of multiple axes (Bertocchini and Stern, 2002; Bertocchini et al., 2004). While many genes are expressed posteriorly at these early stages and are involved in axis formation, only one to date, the transcription factor Gata2, shows a stronger expression anteriorly, decreasing towards the posterior region (Sheng and Stern, 1999).Here, we investigate its role in specification of embryonic polarity. Morpholino mediated knock-down of Gata2 causes upregulation of posterior markers along the circumference of the embryo, or ectopic sites of axis initiation; these embryos then develop an ectopic axis or show a displacement of the endogenous axis. This suggests that Gata2 plays a role in positioning the embryonic axis, and that it somehow inhibits axis formation anteriorly. At very early stages, Gata2 and Vg1 (a member of the TGFb family of signalling molecules) are expre...