Key-notes on Neural Induction
1. Neural Induction
1.1. The neural default model
This model (nowadays considered too simplistic) is based on data obtained from experimental studies mostly performed in Xenopus. When animal cap tissue (tissue situated around the animal-pigmented- pole of a very early gastrula-stage embryo) is explanted and cultured in isolation in vitro it differentiates into epidermis. However, if the animals cap tissue is dissociated in culture, the individual cells differentiate into neurons. This suggested that the default developmental pathway is neural and that epidermal fate arises from a community effect in which molecules produced by the ectoderm itself suppress neural development. Instead, isolated cells do not produce sufficient amounts of these molecules to prevent neural differentiation and thus single cells spontaneously develop into neurons. The role of the organizer is to inhibit these molecules allowing the latent neural potential of the ectoderm to develop.
Several experimental evidences indicate that the key molecular players in the inhibition of neural differentiation of the ectoderm are members of the bone morphogenetic protein (BMP- i.e BMP2, BMP4 and BMP7) family of the TGFbeta superfamily). For example, interfering with BMP signalling pathway by expressing dominant negative BMPs or BMPs receptors, or antisense bmp RNA, results in a dorsalized embryo with all ectodermal cells becoming neural. BMPs play a fundamental role in specifying ventral cell fates in the Xenopus embryo. The effect of BMP signaling is opposed by dorsalizing signals from the organizer. Among anti-BMP proteins with neural inducing activity are: Noggin, Chordin, Follistatin and Cerberus that exert their activity by binding directly to several BMPs with greater affinity compared to the corresponding BMP receptors (competitive inhibition of BMP activity).
Other molecules secreted by the organizer (e.g Xenopus nodal related 3 - Xnr3) exert their inhibitory effect by competing for BMP receptors or shared intracellular signal transduction proteins (SMADs). The competitive inhibition of BMPs by proteins secreted by the organizer results in a gradient of BMP activity from ventral to dorsal in the embryo: in the dorsal ectoderm, where there is low BMP activity, the neural plate is induced.