Making Myelin: The myelin sheath insulates neurons and facilitates rapid axonal conduction, and its disruption is characteristic of some neurological disorders, such as multiple sclerosis. Axonal signals stimulate Schwann cells to form myelin in peripheral nerves, but the mechanism is not completely known. By characterizing a mutation identified in zebrafish, Monk et al. (p. 1402 ; see the Perspective by Meijer ) show that Gpr126, a member of the G protein–coupled receptor superfamily, is essential for myelin formation. It appears that Gpr126 acts as a receptor for axonal signals to elevate cAMP levels in Schwann cells and trigger myelination.

We have isolated a novel secreted molecule, Wise, by a functional screen for activities that alter the anteroposterior character of neuralised Xenopus animal caps. Wise encodes a secreted protein capable of inducing posterior neural markers at a distance. Phenotypes arising from ectopic expression or depletion of Wise resemble those obtained when Wnt signalling is altered. In animal cap assays, posterior neural markers can be induced by Wnt family members, and induction of these markers by Wise requires components of the canonical Wnt pathway. This indicates that in this context Wise activates the Wnt signalling cascade by mimicking some of the effects of Wnt ligands. Activation of the pathway was further confirmed by nuclear accumulation of β-catenin driven by Wise. By contrast, in an assay for secondary axis induction, extracellularly Wise antagonises the axis-inducing ability of Wnt8. Thus, Wise can activate or inhibit Wnt signalling in a context-dependent manner. The Wise protein physically interacts with the Wnt co-receptor, lipoprotein receptor-related protein 6 (LRP6), and is able to compete with Wnt8 for binding to LRP6. These activities of Wise provide a new mechanism for integrating inputs through the Wnt coreceptor complex to modulate the balance of Wnt signalling.

Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGFβ. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGFβ-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis.

Neocorticogenesis in mice homozygous for anEmx2null allele is the topic of this article. The development of both main components of neocortex, primordial plexiform layer derivatives and cortical plate, was analyzed, paying special attention to radial migration of neurons forming the cortical plate. The products of theReelingene, normally playing a key role in orchestrating radial migration of these neurons, display normal distribution at the beginning of the cortical neuronogenesis but are absent in the neocortical marginal zone of the mutant mice at the time when the cortical plate is laid down. As a consequence, the development of radial glia is impaired, and neurons making up the cortical plate display abnormal migration patterns. In addition, restricted defects along the rostrocaudal and the mediolateral axes are present in the subplate, suggesting anEmx2-specific role in priming the proper development of this layer.

The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof/Fezl) in zebrafish. However, how Tof/Fezl regulates the commitment and differentiation of these DA neurons is not known. Proneural genes encoding basic helix–loop–helix transcription factors regulate the development of multiple neuronal lineages, but their involvement in vertebrate DA neuron determination is unclear. Here we show that neurogenin 1 ( ngn1 ), a vertebrate proneural gene related to the Drosophila atonal , is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish. Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the pan-neuronal marker Hu in nonneural ectoderm. We further show that Tof/Fezl is required to establish basal forebrain ngn1 -expressing DA progenitor domains. These findings identify Ngn1 as a determinant of brain DA neurons and provide insights into how Tof/Fezl regulates the development of these clinically important neuronal types.