TY  - JOUR
A1  - Pfeiffer, Verena
A1  - Götz, Rudolf
A1  - Xiang, Chaomei
A1  - Camarero, Guadelupe
A1  - Braun, Attila
A1  - Zhang, Yina
A1  - Blum, Robert
A1  - Heinsen, Helmut
A1  - Nieswandt, Bernhard
A1  - Rapp, Ulf R.
T1  - Ablation of BRaf Impairs Neuronal Differentiation in the Postnatal Hippocampus and Cerebellum
JF  - PLoS ONE
N2  - This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12) but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.
KW  - granule cells
KW  - hippocampus
KW  - neurons
KW  - neuronal dendrites
KW  - embryos
KW  - dentate gyrus
KW  - neuronal differentiation
KW  - cerebellum
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130304
VL  - 8
IS  - 3
ER  - 
TY  - JOUR
A1  - Dusik, Verena
A1  - Senthilan, Pingkalai R.
A1  - Mentzel, Benjamin
A1  - Hartlieb, Heiko
A1  - Wülbeck, Corina
A1  - Yoshii, Taishi
A1  - Raabe, Thomas
A1  - Helfrich-Förster, Charlotte
T1  - The MAP Kinase p38 Is Part of Drosophila melanogaster's Circadian Clock
JF  - PLoS Genetics
N2  - All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. Here, we demonstrate by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, we found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining ∼ 24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed our Western Blot results and point to p38 as a potential "clock kinase" phosphorylating Period. Taken together, our findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways.
KW  - in vitro kinase assay
KW  - biological locomotion
KW  - circadian oscillators
KW  - MAPK signaling cascades
KW  - circadian rhythms
KW  - drosophila melanogaster
KW  - neurons
KW  - phosphorylation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119433
SN  - 1553-7404
VL  - 10
IS  - 8
ER  -