Lectures L5.1 Calcium signalling and gene expression during early neurogenesis in Xenopus laevis Catherine Leclerc 1 , Isabelle Néant 1 , Sarah E. Webb 2 , Andrew L. Miller 2 , Marc Moreau 1 1 Centre de Biologie du Développement, UMR 5547 CNRS/UPS and GDR 2688 Toulouse France; 2 Calcium Aequorin Imaging Lab, HKUST, Hong Kong, People Republic of China e-mail: Catherine Leclerc <leclerc@cict.fr> The formation of the nervous system occurs during gas- trulation, with a process called neural induction. In the past 15 years using amphibians model, it has been suggested that neural induction results from the opposing action of ventralizing signals such as bone morphogenetic proteins (BMPs) from the ectoderm, which are responsible for the determination of the epidermis, and dorsalizing signals, such as noggin, chordin, follistatin, XnR3 and Cerberus, from the dorsal mesoderm. However this mechanism is not suffcient and increasing evidence both from literature and from our data suggests an additional mechanism (Delaune et al., 2005; Moreau et al., 2009; Stern, 2005). Work performed by our team, has clearly demonstrated that neural induction is an instructive process, where an increase in [Ca 2+ ] i , triggered by the activation of dihydropy- ridine-sensitive Ca 2+ channels (DHP-Ca 2+ channels), plays a necessary and suffcient role (Leclerc, et al., 2000; Leclerc. et al., 2003; Batut et al., 2005). We have identifed the key players involved in the Ca 2+ -de- pendent signalling pathways and we present a new model for neural induction. Our model of neural induction inte- grates the activation of a Ca 2+ -dependent signalling path- way due to an infux of Ca 2+ through voltage dependant Ca 2+ channels (Cav1.2). The mechanism by which Cav1.2 are opened might be through the activation of FGF sig- nalling via arachidonic acid formation and TRPC1 channel activation (Lee et al., 2009). References: Batut J, Vandel L, Leclerc C, Daguzan C, Moreau M, Néant I (2005) Proc Natl Acad Sci USA 102: 15128–15133. Delaune E, Lemaire P, Kodjabachian L (2005) Development 132: 299–310. Leclerc C, Lee M, Webb SE, Moreau M, Miller AL (2003) Dev Biol 261: 381–390. Leclerc C, Webb SE, Daguzan C, Moreau M, Miller AL (2000) J Cell Sci 113: 3519–3529. Lee KW, Moreau M, Neant I, Bibonne A, Leclerc C (2009) Biochim Biophys Acta 1793: 1033–1040. Moreau M, Neant I, Webb SE, Miller AL, Leclerc C (2008) Philos Trans R Soc Lond B Biol Sci 363: 1371–1375. Stern CD (2005) Development 132: 2007–2021. L5.2 Alternative splicing and the control of neuronal gene expression Douglas L. Black HHMI/UCLA Department of Microbiology, Immunology, and Molecular Genetics, 6780 MRL, Box 951662 675 Charles Young Dr. S, Los Angeles, CA 90095-1662, USA e-mail: Douglas Black <dougb@microbio.ucla.edu> L-type calcium channel activation and CaM Kinase IV sig- naling alter the splicing of many transcripts encoding ion channels, neurotransmitter receptors, and other synaptic proteins to alter their electrophysiological properties. Some alternative exons that are repressed in the initial phase of chronic depolarization are regulated by regulated by RNA binding proteins of the Fox family. We have shown that, for some exons, Fox-1/A2BP1 can counteract the effect of chronic depolarization on splicing. Exon 19 of Fox-1 is it- self repressed by depolarization. Fox-1 transcripts missing exon 19 encode a nuclear isoform of Fox-1 that progres- sively replaces the cytoplasmic Fox-1 isoform as cells are maintained depolarizing media. The increased nuclear Fox- 1 reactivates of many Fox-1 target exons, including exon 5 of the NMDA receptor 1, that were initially repressed by the high KCl medium. Thus, Fox protein relocalization provides a mechanism for the slow modulation of splicing as cells adapt to chronic stimuli. Among the target exons for Fox proteins are two exons in the L-type calcium chan- nel. We thus fnd a regulatory loop where Calcium signal- ing alters splicing of calcium channels to affect subsequent signaling. Session 5: Calcium and gene expression in diferentiation