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26 The TGF-β Family in Neural and Neuronal Differentiation and Development

Jayshree Samanta, Michael A. Bonaguidi, John A. Kessler


Modulation of signaling by transforming growth factor-β (TGF-β) family members is critical for the formation and function of the nervous system from the earliest stages of embryogenesis through adult life. Sequential waves of activation, inhibition, and reactivation of signaling by TGF-β family members are responsible for the initial induction of the nervous system, dorsalization and establishment of rostral-caudal boundaries, patterning of the developing central nervous system, lineage commitment of neurons and glia, cell migration and axon guidance, synaptogenesis, and cell survival (see Table 1). In the adult nervous system, TGF-β family members are important modulators of inflammatory responses and have a role in a number of degenerative diseases. This chapter discusses the expression, regulation, and function of TGF-β family members in the central nervous system beginning with early development and progressing temporally to adult life. The role of these factors in the neural crest and in neural crest derivatives is discussed in Chapter 21.

Neural induction is the process whereby the neural plate, which gives rise to the entire central nervous system encompassing the brain and spinal cord, is specified within the dorsal ectoderm. This process is initiated in the blastula stage and continues through gastrulation to ultimately specify the neural plate at the expense of epidermal ectoderm (for reviews, see De Robertis and Kuroda 2004; Stern 2005). Neural induction is mediated primarily by inhibition of two key TGF-β family pathways: nodal and activin signaling and bone morphogenetic protein (BMP) signaling (Fig. 1). The study of the signals...

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