The zebrafish has become a new model for adult neurogenesis, owing to its abundant neurogenic areas in most brain subdivisions. Radial glia-like cells, actively proliferating cells, and label-retaining progenitors have been described in these areas. In the telencephalon, this complexity is enhanced by an organization of the ventricular zone (VZ) in fast and slow-dividing domains, suggesting the existence of heterogeneous progenitor types. In this work, we studied the expression of various transgenic or immunocytochemical markers for glial cells (gfap:gfp, cyp19a1b:gfp, BLBP, and S100beta), progenitors (nestin:gfp and Sox2), and neuroblasts (PSA-NCAM) in cycling progenitors of the adult zebrafish telencephalon (identified by expression of proliferating cell nuclear antigen (PCNA), MCM5, or bromodeoxyuridine incorporation). We demonstrate the existence of distinct populations of dividing cells at the adult telencephalic VZ. Progenitors of the overall slow-cycling domains express high levels of Sox2 and nestin:gfp as well as all glial markers tested. In contrast, domains with an overall fast division rate are characterized by low or missing expression of glial markers. PCNA-positive cells in fast domains further display a morphology distinct from radial glia and co-express PSA-NCAM, suggesting that they are early neuronal precursors. In addition, the VZ contains cycling progenitors that express neither glial markers nor nestin:gfp, but are positive for Sox2 and PSA-NCAM, identifying them as committed neuroblasts. On the basis of the marker gene expression and distinct cell morphologies, we propose a classification for the dividing cell states at the zebrafish adult telencephalic VZ.

Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here.

In contrast to mammals, the brain of the adult zebrafish has a remarkable ability to regenerate. In mammals, injuries induce proliferation of astrocytes and oligodendrocyte progenitors contributing to the formation of a glial scar. We analyzed the proliferation of glial cells and microglia in response to stab injury in the adult zebrafish telencephalon: Radial glial markers were up-regulated at the ventricle and coexpressed the proliferation nuclear antigen (PCNA). Microglia and oligodendrocyte progenitors accumulated transiently at the site of lesion. However, we could not find evidence of permanent scar formation. Parenchymal proliferation was almost negligible in comparison to the increase in proliferation at the ventricular zone. This suggests that most of the cellular material for regeneration is derived from regions of constitutive neurogenesis. Remarkably, the proliferative response is almost completely restricted to the lesioned hemisphere indicating that signals inducing regeneration remain mainly confined within the lesioned half of the telencephalon. Developmental Dynamics 240:2221-2231,

Adult neurogenesis arises from niches that harbor neural stem cells (NSC). Although holding great promise for regenerative medicine, the identity of NSC remains elusive. In mammals, a key attribute of NSC is the expression of the filamentous proteins glial fibrillary acidic protein (GFAP) and NESTIN. To assess whether these two markers are relevant in the fish model, two transgenic zebrafish lines for gfap and nestin were generated. Analysis of adult brains showed that the fusion GFAP-green fluorescent protein closely mimics endogenous GFAP, while the nestin transgene recapitulates nestin at the ventricular zones. Cells expressing the two reporters display radial glial morphology, colocalize with the NSC marker Sox2, undergo proliferation, and are capable of self-renewal within the matrix of distinct thickness in the telencephalon. Together, these two transgenic lines reveal a conserved feature of putative NSC in the adult zebrafish brain and provide a means for the identification and manipulation of these cells in vivo. Developmental Dynamics 238:475-486, 2009.

In contrast to adult vertebrates, which have limited capacities for neurogenesis, adult planarians undergo constitutive cellular turnover during homeostasis and are even able to regenerate a whole brain after decapitation. This enormous plasticity derives from pluripotent stem cells residing in the planarian body in large numbers. It is still obscure how these stem cells are programmed for differentiation into specific cell lineages and how lineage identity is maintained. Here we identify a Pitx transcription factor of crucial importance for planarian regeneration. In addition to patterning defects that are co-dependent on the LIM homeobox transcription factor gene islet1, which is expressed with pitx at anterior and posterior regeneration poles, RNAi against pitx results in islet1-independent specific loss of serotonergic (SN) neurons during regeneration. Besides its expression in terminally differentiated SN neurons we found pitx in stem cell progeny committed to the SN fate. Also, intact pitx RNAi animals gradually lose SN markers, a phenotype that depends neither on increased apoptosis nor on stem cell-based turnover or transdifferentiation into other neurons. We propose that pitx is a terminal selector gene for SN neurons in planarians that controls not only their maturation but also their identity by regulating the expression of the Serotonin production and transport machinery. Finally, we made use of this function of pitx and compared the transcriptomes of regenerating planarians with and without functional SN neurons, identifying at least three new neuronal targets of Pitx.KEY WORDS: Planaria, Schmidtea mediterranea, Regeneration, Serotonergic neuron, Pitx, Islet1, Stem cell differentiation INTRODUCTIONTranscription factors are key regulators of differentiation processes and the misexpression of a small number of transcription factors can change the fate of a cell completely (reviewed by Sancho-Martinez et al., 2012). The family of paired class homeobox/pituitary homeobox (Pitx) transcription factors has been implicated in a number of differentiation decisions in mammals. For instance, Pitx proteins can act as terminal selectors, which are transcription factors that regulate both the terminal differentiation of a late progenitor cell and the establishment and maintenance of its cell type-specific functions (reviewed by Flames and Hobert, 2011;Hobert, 2011; RESEARCH ARTICLE STEM CELLS AND REGENERATIONMax Planck Research Group Stem Cells and Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Münster, Germany.*Author for correspondence (kerstin.bartscherer@mpi-muenster.mpg.de) This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.Received 20 February 2013; Accepted 22 August 2013 Hobert et al., 2010). In the mouse, Pitx2 and Pitx3 ar...