Marta de Almeida, I.; (2012) Searching for novel neural inducing signals. Doctoral thesis , UCL (University College London).

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Abstract

Neural induction marks the beginning of vertebrate nervous system formation, consisting of an interaction between the organizer, which emits inducing signals, and the ectoderm, which responds by giving rise to the neural plate. In the present study we explored the role of FGF signals, Wnt inhibition and BMP inhibition in chick neural induction. Contrasting with previous work, in vivo studies in the extraembryonic ectoderm revealed that FGF signals, even together with inhibition of Wnts and BMPs are not capable of causing the surrounding cells to acquire a neural character. Inhibition of BMPs can, however, extend the border of the neural plate. To uncover possible missing factors secreted by the organizer, a screen to isolate cDNAs encoding for secreted proteins was carried out. 442 clones were obtained and, after blast analyses, 137 were selected to be put through an in situ hybridization screen, narrowing down the number of candidate molecules to 23. Of these, and based on their expression in the node and/or anterior primitive streak, 3 were studied further, including cloning, molecular characterization and functional analysis in the context of neural induction in the chick embryo. Fibulin2 belongs to the Fibulin family of extracellular matrix proteins. Our results suggest that is not directly involved in neural induction. Calreticulin is largely present in the endoplasmic reticulum, and widely studied as an intracellular calcium regulator. We report that it can be secreted and acts like a BMP inhibitor, extending the border of the neural plate and rescuing the effect of BMP overexpression. It cannot, however, induce neural character in the competent extraembryonic ectoderm. Nhbr90 seems not to be translated but act as a RNA. It is the first molecule identified with the ability of inducing the neural marker Sox2 in the extraembryonic ectoderm. The work presented emphasises the complexity of the neural induction process and that we are only beginning to understand how the molecular players interact to form an early neural plate.

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