This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.neuraldevelopment.com The latest articles from Neural Development (ISSN 1749-8104) published by BioMed Central Background: Wnt proteins comprise a large class of signaling molecules that regulate a variety of developmental processes, including synapse formation. Previous studies have shown Wnts to be involved in both the induction and prevention of synapses in a number of different organisms. However, it is not clear whether the influence of Wnts on synapses is a result of Wnts' behaviour in different organisms or differences in the activity of different Wnt ligands. Results: We used in situ hybridization to show that several Wnt ligands (Wnt3, Wnt5a, Wnt7a, and Wnt7b) and their receptors, Frizzled, are expressed in the developing hippocampus during the period of synapse formation in rodents. We used recombinant Wnt protein or Wnt conditioned media to explore the effects of Wnts on synapses in hippocampal cultures. We found that Wnt7a and Wnt7b activate canonical signalling, whereas Wnt5a activates a noncanonical pathway. The activation of the canonical pathway, either through pathway manipulations or through Wnt stimulation, increases presynaptic inputs. In contrast, exposure to Wnt5a, which activates a noncanonical signalling pathway, decreases the number of presynaptic terminals. Conclusions: Our observations suggest that the pro- and antisynaptogenic effects of Wnt proteins are associated with the activation of the canonical and noncanonical Wnt signalling pathways. http://www.neuraldevelopment.com/content/3/1/32 Elizabeth K. Davis, Yimin Zou and Anirvan Ghosh Neural Development 2008, 3:32 2008-11-05 doi:10.1186/1749-8104-3-32 Neural Development 1749-8104 3 32 2008-11-05 After publication of this work [1], we noted that we inadvertently failed to include the complete list of all co-authors. The full list of authors has now been added and the Authors' contributions and Competing interests section modified accordingly. http://www.neuraldevelopment.com/content/3/1/31 Ugo Borello, Inma Cobos, Jason E Long, John R McWhirter, Cornelis Murre and John LR Rubenstein Neural Development 2008, 3:31 2008-11-05 doi:10.1186/1749-8104-3-31 Neural Development 1749-8104 3 31 2008-11-05 Background: Radial glia comprise a molecularly defined neural progenitor population but their role in neurogenesis has remained contested due to the lack of a single universally accepted genetic tool for tracing their progeny and the inability to distinguish functionally distinct developmental stages. Results: By direct comparisons of Cre/loxP lineage tracing results obtained using three different radial glial promoters (Blbp, Glast, and hGFAP) , we show that most neurons in the brain are derived from radial glia. Further, we show that hGFAP promoter induction occurs in ventral telencephalic radial glia only after they have largely completed neurogenesis. Conclusions: These data establish the major neurogenic role of radial glia in the developing central nervous system and genetically distinguish an early neurogenic Blbp+Glast+hGFAP- stage from a later gliogenic Blbp+Glast+hGFAP+ stage in the ventral telencephalon. http://www.neuraldevelopment.com/content/3/1/30 Todd E Anthony and Nathaniel Heintz Neural Development 2008, 3:30 2008-11-05 doi:10.1186/1749-8104-3-30 Neural Development 1749-8104 3 30 2008-11-05 Background: Robo1, Robo2 and Rig-1 (Robo3), members of the Robo protein family, are candidate receptors for the chemorepellents Slit and are known to play a crucial role in commissural axon guidance in the spinal cord. However, their roles at other axial levels remain unknown. Here we examine expression of Robo proteins by cerebellofugal (CF) commissural axons in the rostral hindbrain and investigate their roles in CF axon pathfinding by analysing Robo knockout mice. Results: We analysed the expression of Robo proteins by CF axons originating from deep cerebellar neurons in rodent embryos, focusing on developmental stages of their midline crossing and post-crossing navigation. At the stage of CF axon midline crossing, mRNAs of Robo1 and Robo2 are expressed in the nuclear transitory zone of the cerebellum, where the primordium of the deep cerebellar nuclei are located, supporting the notion that CF axons express Robo1 and Robo2. Indeed, immunohistochemical analysis of CF axons labelled by electroporation to deep cerebellar nuclei neurons indicates that Robo1 protein, and possibly also Robo2 protein, is expressed by CF axons crossing the midline. However, weak or no expression of these proteins is found on the longitudinal portion of CF axons. In Robo1/2 double knockout mice, many CF axons reach the midline but fail to exit it. We find that CF axons express Rig-1 (Robo3) before they reach the midline but not after the longitudinal turn. Consistent with this in vivo observation, axons elicited from a cerebellar explant in co-culture with a floor plate explant express Rig-1. In Rig-1 deficient mouse embryos, CF axons appear to project ipsilaterally without reaching the midline. Conclusions: These results indicate that Robo1, Robo2 or both are required for midline exit of CF axons. In contrast, Rig-1 is required for their approach to the midline. However, post-crossing up-regulation of these proteins, which plays an important role in spinal commissural axon guidance, does not appear to be required for the longitudinal navigation of CF axons after midline crossing. Our results illustrate that although common mechanisms operate for midline crossing at different axial levels, significant variation exists in post-crossing navigation. http://www.neuraldevelopment.com/content/3/1/29 Atsushi Tamada, Tatsuro Kumada, Yan Zhu, Tomoko Matsumoto, Yumiko Hatanaka, Keiko Muguruma, Zhe Chen, Yasuto Tanabe, Makio Torigoe, Kenta Yamauchi, Hiroshi Oyama, Kazuhiko Nishida and Fujio Murakami Neural Development 2008, 3:29 2008-11-05 doi:10.1186/1749-8104-3-29 Neural Development 1749-8104 3 29 2008-11-05 Background: Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs) emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results: We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased. Conclusion: BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype. http://www.neuraldevelopment.com/content/3/1/28 Katrin Huber, Aylin Franke, Barbara Brühl, Shlomi Krispin, Uwe Ernsberger, Andreas Schober, Oliver von Bohlen und Halbach, Hermann Rohrer, Chaya Kalcheim and Klaus Unsicker Neural Development 2008, 3:28 2008-10-22 doi:10.1186/1749-8104-3-28 Neural Development 1749-8104 3 28 2008-10-22 Background: Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results: We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion: Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion. http://www.neuraldevelopment.com/content/3/1/27 Maya Groysman, Irit Shoval and Chaya Kalcheim Neural Development 2008, 3:27 2008-10-22 doi:10.1186/1749-8104-3-27 Neural Development 1749-8104 3 27 2008-10-22 Background: Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear. Results: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity. Conclusion: We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes. http://www.neuraldevelopment.com/content/3/1/26 Pei-I Tsai, Hsiu-Hua Kao, Caroline Grabbe, Yu-Tao Lee, Aurnab Ghose, Tzu-Ting Lai, Kuan-Po Peng, David Van Vactor, Ruth H Palmer, Ruey-Hwa Chen, Shih-Rung Yeh and Cheng-Ting Chien Neural Development 2008, 3:26 2008-10-16 doi:10.1186/1749-8104-3-26 Neural Development 1749-8104 3 26 2008-10-16 Background: The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β) superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results: Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion: The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice. http://www.neuraldevelopment.com/content/3/1/25 Katharina Heupel, Vardanush Sargsyan, Jaap J Plomp, Michael Rickmann, Frédérique Varoqueaux, Weiqi Zhang and Kerstin Krieglstein Neural Development 2008, 3:25 2008-10-14 doi:10.1186/1749-8104-3-25 Neural Development 1749-8104 3 25 2008-10-14 Background: The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2. Results: In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen-2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three. Conclusion: All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction. http://www.neuraldevelopment.com/content/3/1/24 Michael A Fox, Matthew SP Ho, Neil Smyth and Joshua R Sanes Neural Development 2008, 3:24 2008-09-25 doi:10.1186/1749-8104-3-24 Neural Development 1749-8104 3 24 2008-09-25 Background: Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. Results: We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. Conclusion: This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1. http://www.neuraldevelopment.com/content/3/1/23 Joanne SM Kim, Brendan N Lilley, Chao Zhang, Kevan M Shokat, Joshua R Sanes and Mei Zhen Neural Development 2008, 3:23 2008-09-22 doi:10.1186/1749-8104-3-23 Neural Development 1749-8104 3 23 2008-09-22