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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.04.034 Byline: Toshiaki Okada (a), Yuki Okumura (a), Jun Motoyama (b), Masaharu Ogawa (a) Keywords: FGF8; Telencephalon; Midline; Transcription factor; Mouse Abstract: FGF8 has been reported to act as a primary regulator of neocortical patterning along the anteroposterior (AP) axis in the mouse telencephalon, and disruption of FGF signaling causes distortion of molecular arealization along the AP axis. Since hypoplasia of midline structures is observed in Fgf8 mutant mice, FGF8 is also postulated to be involved in telencephalic midline development. In this study we analyzed the role of FGF8 in midline development by means of gain-of-function and loss-of-function experiments. The results showed that FGF8 up-regulates the expression of transcription factor (TF) genes, including putative key factors involved in midline development. Although FGF8 had been thought to act downstream of SHH signaling, ectopic FGF8 up-regulates the expression of midline TF genes in Shh null mice, suggesting that FGF signaling acts as an upstream positive regulator of midline TFs during midline development independently of SHH. Author Affiliation: (a) Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan (b) Molecular Neuropathology Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan Article History: Received 15 November 2007; Revised 21 April 2008; Accepted 24 April 2008

Research has been conducted on homeodomain proteins Brn-1 and Brn-2 coexpressed in the developing neocortex. Results indicate that the double disruption of Brn-1 and Brn-2 genes leads to the abnormal neocortex formation.

Author(s): Masahisa Yamada [1, 2]; Tsuyoshi Miyakawa [3, 4]; Alokesh Duttaroy [1]; Akihiro Yamanaka [5]; Toru Moriguchi [6]; Ryosuke Makita [2]; Masaharu Ogawa [2]; Chieh J. Chou [7]; Bing Xia [...]

Results demonstrate that Cadherin-related neuronal proteins (CNR) function as multiple receptors for signal transduction mediated by Reelin in the central nervous system. Data further point out that the number of CNR genes containing Reelin-binding domains vary across terrestrial vertebrates.

There is increasing interest in the role of RNA-binding proteins during neural development. Drosophila Musashi is one of the neural RNA-binding proteins essential for neural development and required for asymmetric cell divisions in the Drosophila adult sensory organ development. Here, a novel mammalian neural RNA-binding protein, mouse-Musashi-1, was identified based on the homology to Drosophila Musashi and Xenopus NRP-1. In the developing CNS, mouse-Musashi-1 protein was highly enriched in the CNS stem cell. Single-cell culture experiments indicated that mouse-Musashi-1 expression is associated with neural precursor cells that are capable of generating neurons and glia. In contrast, in fully differentiated neuronal and glial cells mouse-Musashi-1 expression is lost. This expression pattern of mouse-Musashi-1 is complementary to that of another mammalian neural RNA-binding protein, Hu (a mammalian homologue of a Drosophila neuronal RNA-binding protein Elav), that is expressed in postmitotic neurons within the CNS. In vitro studies indicated that mouse-Musashi-1 possesses binding preferences on poly(G) RNA homopolymer, whereas Hu is known to preferentially bind to short A/U-rich regions in RNA. Based on their differential expression patterns and distinct preferential target RNA sequences, we believe that the mouse-Musashi-1 and Hu proteins may play distinct roles in neurogenesis, either through sequential regulatory mechanisms or differential sorting of mRNA populations during asymmetric division of neural precursor cells.

Abstract Background Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated. Results We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step. Conclusions Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.