Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.

Wingless-related MMTV integration site 1 (WNT1)/β-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons, including the substantia nigra pars compacta (SNc) subpopulation that preferentially degenerates in Parkinson's disease (PD). However, the precise functions of WNT1/β-catenin signaling in this context remain unknown. Stem cell-based regenerative (transplantation) therapies for PD have not been implemented widely in the clinical context, among other reasons because of the heterogeneity and incomplete differentiation of the transplanted cells.

FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.

The normal cellular organization and layering of the vertebrate cerebellum is established during embryonic and early postnatal development by the interplay of a complex array of genetic and signaling pathways. Disruption of these processes and of the proper layering of the cerebellum usually leads to ataxic behaviors. Here, we analyzed the relative contribution of Fibroblast growth factor receptor 2 (FGFR2)-mediated signaling to cerebellar development in conditional Fgfr2 single mutant mice.

Nitrogen deposition along differently exposed slopes in the Bavarian Alps.

The Alps are affected by high nitrogen deposition, particularly in the fringe of the Northern and Southern Alps. In the framework of a two-year monitoring study performed in 2010 and 2011, we investigated the ammonia and nitrogen dioxide air concentration and ammonium and nitrate deposition at different altitudes between 700 and 1,600 ma.s.

Are mouse lens epithelial cells more sensitive to γ-irradiation than lymphocytes?

In this pilot study we compared for the first time the radiation sensitivity of mouse lens epithelial cells (LECs) and mouse lymphocytes. We freshly prepared LECs and lymphocytes and irradiated them with γ-rays ((137)Cs; doses ranging from 0.25 to 2 Gy).

Feedback inhibition of the general phenylpropanoid and flavonol biosynthetic pathways upon a compromised flavonol-3-O-glycosylation.

Flavonols, phenylalanine-derived secondary metabolites, have protective and regulatory functions in plants. In Arabidopsis thaliana, they are consecutively glycosylated at their 3-OH and 7-OH groups. UGT78D1 and UGT78D2 are the major flavonol 3-O-glycosyltransferases in Arabidopsis leaves.

The Arabidopsis glucosyltransferase UGT76B1 conjugates isoleucic acid and modulates plant defense and senescence.

Plants coordinate and tightly regulate pathogen defense by the mostly antagonistic salicylate (SA)- and jasmonate (JA)-mediated signaling pathways. Here, we show that the previously uncharacterized glucosyltransferase UGT76B1 is a novel player in this SA-JA signaling crosstalk. UGT76B1 was selected as the top stress-induced isoform among all 122 members of the Arabidopsis thaliana UGT family.

Modulation of Fgfr1a signaling in zebrafish reveals a genetic basis for the aggression-boldness syndrome.

Behavioral syndromes are suites of two or more behaviors that correlate across environmental contexts. The aggression-boldness syndrome links aggression, boldness, and exploratory activity in a novel environment. Although aggression-boldness has been described in many animals, the mechanism linking its behavioral components is not known.

Fgf15-mediated control of neurogenic and proneural gene expression regulates dorsal midbrain neurogenesis.

The balanced proliferation and cell cycle exit of neural progenitors, by generating the appropriate amount of postmitotic progeny at the correct time and in the proper location, is required for the establishment of the highly ordered structure of the adult brain. Little is known about the extrinsic signals regulating these processes, particularly in the midbrain. Fibroblast growth factor (Fgf) 15, the mouse ortholog of FGF19 and member of an atypical Fgf subfamily, is prominently expressed in the dorsolateral midbrain of the midgestational mouse embryo.

Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells.

The limited generation of neurons during adulthood is controlled by a balance between quiescence and recruitment of neural stem cells (NSCs). We use here the germinal zone of the zebrafish adult telencephalon to examine how the frequency of NSC divisions is regulated. We show, using several in vivo techniques, that progenitors transit back and forth between the quiescent and dividing state, according to varying levels of Notch activity: Notch induction drives progenitors into quiescence, whereas blocking Notch massively reinitiates NSC division and subsequent commitment toward becoming neurons.

Semaphorin 3A-Neuropilin-1 signaling regulates peripheral axon fasciculation and pathfinding but not developmental cell death patterns.

In early development, an excess of neurons is generated, of which later about half will be lost by cell death due to a limited supply of trophic support by their respective target areas. However, some of the neurons die when their axons have not yet reached their target, thus suggesting that additional causes of developmental cell death exist. Semaphorin 3A (Sema3A), in addition to its function as a guidance cue and mediator of timing and fasciculation of motor and sensory axon outgrowth, can also induce death of sensory neurons in vitro.

Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect.

Wnt/beta-catenin signaling controls the proper development of the mid-/hindbrain region (MHR) and of midbrain dopaminergic (mDA) neurons, but the Frizzled (Fzd) receptors transducing these signals are still unknown. Fzd3 is expressed throughout the mouse anterior neural tube, whereas Fzd6 is restricted to the MHR. We show that the MHR is properly established and mDA neurons develop normally in Fzd6(-/-) mutants, but the number of mDA neurons is initially reduced and recovers at later stages in Fzd3(-/-) embryos.

GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus.

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signaling pathways. Here, we investigate the role of cAMP response element-binding protein (CREB) signaling in adult hippocampal neurogenesis.

Impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ and C57BL/6J mice.

Housing conditions are known to influence laboratory animal behavior. However, it is not known whether housing mice in individually ventilated cages (IVCs) to maintain optimal hygienic conditions alters behavioral baselines established in conventional housing. This issue is important with regard to comparability and reproducibility of data.

Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic.

Neurological and psychiatric disorders are among the most common and most serious health problems in developed countries. Transgenic mouse models mimicking human neurological diseases have provided new insights into development and function of the nervous system. One of the prominent goals of the German National Genome Research Network is the understanding of the in vivo function of single genes and the pathophysiological and clinical consequences of respective mutations.