Roof Plate in Cerebellar Neurogenesis
The roof plate is a distinct group of cells located at the dorsal midline of the developing central nervous system extending along its entire anterior–posterior axis. In the developing hindbrain, the roof plate comprises a simple epithelial layer covering
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Roof Plate in Cerebellar Neurogenesis Victor V. Chizhikov
Abstract
The roof plate is a distinct group of cells located at the dorsal midline of the developing central nervous system extending along its entire anterior–posterior axis. In the developing hindbrain, the roof plate comprises a simple epithelial layer covering the dorsal opening of the 4th ventricle. As development proceeds, the 4th ventricle roof plate differentiates into choroid plexus epithelium, which produces cerebrospinal fluid and serves as a blood-cerebrospinal fluid barrier. A growing amount of evidence indicates that both the 4th ventricle roof plate and its later derivative, the hindbrain choroid plexus, produce various secreted molecules, which critically regulate development of the adjacent cerebellum. Bone morphogenetic proteins secreted from the roof plate are crucial to the induction of the cerebellar rhombic lip. Signals from the early roof plate and later secretion of Sonic hedgehog from the choroid plexus promote proliferation of progenitors in the cerebellar ventricular zone. This chapter discusses recent studies that established the roles of the 4th ventricle roof plate and the hindbrain choroid plexus in cerebellar neurogenesis and the molecular mechanisms of their action.
Introduction During development, neurogenesis in many regions of the central nervous system is regulated by secreted signals produced by specialized groups of cells called signaling centers (Lee and Jessell 1999; Kiecker and Lumsden 2005; Sillitoe and Joyner 2007; Dessaud et al. 2008). One such signaling center regulating cerebellar development is the isthmic organizer (IsO), located at the mid-hindbrain boundary.
V.V. Chizhikov Center for Integrative Brain Research, Seattle Children’s Hospital Research Institute, 1900, 9th Avenue, Mailstop C9S-10, Seattle, WA 98101, USA e-mail: [email protected] M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_4, # Springer Science+Business Media Dordrecht 2013
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As discussed earlier in this book (▶ Chap. 1, “Specification of the Cerebellar Territory”), numerous studies have demonstrated that fibroblast growth factor (FGF) signals secreted from the IsO are important for proper establishment of the cerebellar territory during early developmental stages. More recently, another embryonic structure, the 4th ventricle roof plate and its later derivative, the hindbrain choroid plexus, have emerged as additional signaling centers regulating multiple aspects of cerebellar neurogenesis. The roof plate is a transient embryonic signaling center located at the dorsal midline of the developing central nervous system along its entire anterior-posterior axis (Lee and Jessell 1999; Monuki et al. 2001; Chizhikov and Millen 2005; Wilson and Maden 2005; Cheng et al. 2006; He´bert and Fishell 2008). At most levels of the neural tube, along the anterior–posterior axis, it appears as a dorsal stripe of
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