A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54

Europa im Geflecht der Welt

Der Band dokumentiert Vorträge und Workshops der internationalen Abschlusstagung des DFG-Schwerpunktprogrammes 1173 „Integration und Desintegration der Kulturen im europäischen Mittelalter“, die Ende Mai 2011 in Berlin stattgefunden hat. Bei der Arbeit im Schwerpunktprogramm hatte sich gezeigt, wie schwierig es ist, Europa im geographischen und historischen Sinne vom Mittelmeerraum mit Nordafrika und Vorder¬asien zu trennen. Daher wurden die Grenzen des mittelalterlichen Europa bewusst überschritten und auch die Geschichte weiter entfernter Länder in den Blick genommen. Als thematischer Schwerpunkt boten sich in diesem Zusammenhang Migrationen an. Migrationen sind ja ein globales Phäno¬men, das an allen Orten und zu allen Zeiten immer wieder die Geschichte der Menschheit prägt und dabei unvermeidlich – selbst in der scheinbaren Isolation einer „Diaspora“ oder „Parallelgesellschaft“ – zu transkulturellen Verflechtungen führt. Fremde und einheimische Gruppen und Individuen werden in neue soziale Umgebungen gerückt und Kontakte oder Konflikte zwischen ihnen erzeugt. Wo aber das jeweilige Leben gegeneinander abgeschottet werden soll, verliert Kultur ihre Inno¬vations¬kraft und versteinert die Gesellschaft. Mit dem Sachthema der „Migrationen“ und mit einem Blick weit über Europa hinaus, bis nach Amerika, Japan und ins südliche Afrika, wird der Übergang von einer eurozentrierten Mittelalterforschung zu einer transdisziplinären Mediävistik in globalen Zusammenhängen markiert

Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression

Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations