**Author details**

Tanja Vogel

Dept. of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Germany

### **References**


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**Nomenclature and abbreviations**

62 Trends in Cell Signaling Pathways in Neuronal Fate Decision

tricular zone, TF - Transcription factor.

**Acknowledgements**

review.

**Author details**

University Freiburg, Germany

Tanja Vogel

**References**

CA - Cornu ammonis, CGN - Cerebellar granule neurons, CGP - Cerebellar granule precursor, CNS - Central nervous system, CSF - Cerebrospinal fluid, DG - dentate gyrus, ESC - Embryonic Stem Cell, GH - Growth hormone, IIS - Insulin/Igf-signalling, Igf - Insulin like growth factor 1, Igfbp - Insulin like growth factor binding protein, Ir - Insulin receptor, mTOR - mammalian target of rapamycin, NSC - Neural Stem Cell, NPC - Neural Progenitor cell, OB - Olfactory Bulb, OBSC - Olfactory Bulb stem cell, p - phospho-, SGZ - Subgranular zone, SVZ - Subven‐

The author gratefully thanks Dr. K. Thedieck, Dept. of Biology III, Albert-Ludwigs-University Freiburg for conceptualising and discussing this review. I also thank S. Wahane, Dept. of Molecular Embryology, Albert-Ludwigs-University Freiburg for preparing figures for this

Dept. of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-

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**Chapter 3**

**The Role of Smad Proteins for Development,**

Uwe Ueberham and Thomas Arendt

http://dx.doi.org/10.5772/54532

**1. Introduction**

terminal serine residues.

Additional information is available at the end of the chapter

**Differentiation and Dedifferentiation of Neurons**

The development of the nervous system, neuralization of ectodermal cells, specification of cell types as well as generation of neurological diseases are closely linked to Smad proteins, which play a central role by integrating TGFβ and BMP signalling with other essential pathways. Due to new findings on Smad activity in neurons and the nervous system, which comprises new roles for brain plasticity and functions, independent of the canonical signalling pathways, we reconsider their relevance for neuronal differentiation and dedifferentiation processes and as therapeutic targets for treatment of neurological diseases. In this chapter we develop a view at Smad molecules, which attributes them a basic significance and allow proving their specific contextual molecular, cellular and tissue relationships. In order to facilitate the understanding of the complex Smad network in the nervous system an overview of the canonical Smad

Smads are phylogenetic old proteins, which are mediating intracellular signalling of the large group of solube TGFβ ligands (Figure 1), containing transforming growth factor βs (TGFβs), bone morphogentic proteins (BMPs), growth and differentiation factors (GDFs), Müllerian inhibitory factors (MISs), activins and inhibins [4]. Ligand binding to activated heteromeric receptor complexes, recruited from seven type I and five type II serine/threonine receptors, results in the specific phosphorylation of receptor-associated Smads (R-Smads) at two C-

Activin, nodal and TGFβ activate R-Smad2 and 3, while BMP acts by R-Smad1,5 and 8 phosphorylation. In the cytoplasm non-phosphorylated R-Smads are sequestrated by inter‐ acting with specific retention proteins e.g. SARA (Smad anchor for receptor activation) [5], endofin [8], tubulin [3], actin, myosin [11] or filamin [12]. Inhibitory Smad(I-Smad)6 and 7 negatively regulate R-Smad signalling by competing for binding to activated type I receptor and inhibiting R-Smad phosphorylation. I-Smads can also prevent R-Smad complexing to the

> © 2013 Ueberham and Arendt; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Ueberham and Arendt; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

signalling pathway is briefly summarized in the following paragraph.
