Obwohl Identitätsentwicklung und Ablösung-Individuation in Eltern-Kind Beziehungen als verbundene Aufgaben psychosozialer Reifung gelten, sind sie in der psychologischen Forschung relativ unabhängig voneinander behandelt worden. Darüber hinaus sind Langzeitstudien im jungen Erwachsenenalter selten, obwohl sich hier Autonomie und Identität voll entwickeln und qualitative Veränderungen in Eltern-Kind Beziehungen stattfinden. Aus diesem Grund umfasst die vorliegende Dissertation eine differenzierte, dynamisch-entwicklungsbezogene Integration von Eltern-Kind Beziehungen und Identitätsentwicklung im Übergang zum Erwachsenenalter, die sequentielle und reziproke Zusammenhänge zwischen Komponenten, Mechanismen, die diese Zusammenhänge erklären und Determinanten interindividueller Entwicklungsunterschiede beschreibt. In einer längsschnittlichen Untersuchung an Studierenden, wurden die vorgeschlagenen Zusammenhänge getestet. Zusammenhänge zwischen agentischen Eigenschaften, reifer Verbundenheit mit Eltern und Identitätssicherheit zeigten das vorhergesagte Muster reziproker Verstärkung, indiziert durch die Vorhersage eines Anstiegs in Verbundenheit durch Selbstwirksamkeitsüberzeugungen und reziproke Assoziationen zwischen Verbundenheit und Sicherheit bezüglich / Identifikation mit Identitäts-Commitments. Abgelöstheit von Eltern und Identitätsunsicherheit waren relativ unabhängig voneinander. Es wurde argumentiert, dass eine situationsspezifischere Messung eventuell stärkere Zusammenhänge hervorbringt, da stressvolle Situationen kurzfristige Selbstunsicherheiten erzeugen und Annährungsverhalten auslösen. Es wurden Vorschläge gemacht, wie zukünftige Forschung auf diesen Ergebnissen aufbauen könnte, indem sie die vorgeschlagenen Sequenzen und Mechanismen unter Nutzung von Langzeitstudien mit multiplen Messzeitpunkten über Adoleszenz und junges Erwachsenenalter hinweg testet und Eltern als interaktive Agenten mit eigenen Identitäts- und Ablösungsthematiken einbezieht. / Although identity development and separation-individuation in parent-child relationships are widely perceived as related tasks of psychosocial maturation, they have been treated relatively independently in psychological research. Furthermore, longitudinal investigations in young adulthood are very scarce although this is the age period where autonomy and personal identity fully develop and significant, qualitative changes in parent-child relationships take place. Therefore, the present dissertation covers the proposition of a differentiated, dynamic-developmental integration of parent-child relationships and identity development in the transition to adulthood that describes sequential and reciprocal associations between components of identity and relationships, mechanisms that could explain these associations, and determinants of interpersonal differences in development. In a 2-Wave longitudinal study on young adult students, the proposed longitudinal associations were tested. Associations between personal Agency, Mature Connectedness with parents, and Identity certainty showed the predicted pattern of reciprocal reinforcement, indicated by the prediction of an increase in Mature Connectedness by self-efficacy beliefs and by reciprocal associations between Mature Connectedness and certainty about and identification with identity commitments. Separateness and identity uncertainty were relatively independent. It was argued that a more situation-specific and short-termed measurement might provide stronger association because stressful situations might cause momentary self-uncertainty and trigger affiliation-seeking. Recommendations were offered on how future research might extend upon these results by testing the proposed sequences and mechanisms using longitudinal studies with multiple assessment points across the adolescent and young adult years and by incorporating parents as interactive agents with their own identity and separation issues.

Neurogenesis in the adult hippocampus contributes to learning and memory in the healthy brain but is dysregulated in metabolic and neurodegenerative diseases. The molecular relationships between neural stem cell activity, adult neurogenesis, and global metabolism are largely unknown. Here we applied unbiased systems genetics methods to quantify genetic covariation among adult neurogenesis and metabolic phenotypes in peripheral tissues of a genetically diverse family of rat strains, derived from a cross between the spontaneously hypertensive (SHR/OlaIpcv) strain and Brown Norway (BN-Lx/Cub). The HXB/BXH family is a very well established model to dissect genetic variants that modulate metabolic and cardiovascular diseases and we have accumulated deep phenome and transcriptome data in a FAIR-compliant resource for systematic and integrative analyses. Here we measured rates of precursor cell proliferation, survival of new neurons, and gene expression in the hippocampus of the entire HXB/BXH family, including both parents. These data were combined with published metabolic phenotypes to detect a neurometabolic quantitative trait locus (QTL) for serum glucose and neuronal survival on Chromosome 16: 62.1–66.3 Mb. We subsequently fine-mapped the key phenotype to a locus that includes the Telo2-interacting protein 2 gene (Tti2)—a chaperone that modulates the activity and stability of PIKK kinases. To verify the hypothesis that differences in neurogenesis and glucose levels are caused by a polymorphism in Tti2, we generated a targeted frameshift mutation on the SHR/OlaIpcv background. Heterozygous SHR-Tti2+/- mutants had lower rates of hippocampal neurogenesis and hallmarks of dysglycemia compared to wild-type littermates. Our findings highlight Tti2 as a causal genetic link between glucose metabolism and structural brain plasticity. In humans, more than 800 genomic variants are linked to TTI2 expression, seven of which have associations to protein and blood stem cell factor concentrations, blood pressure and frontotemporal dementia.

Cerebellar organization and function have been studied in numerous species of fish. Fish models such as goldfish and weakly electric fish have led to important findings about the cerebellar architecture, cerebellar circuit physiology and brain evolution. However, most of the studied fish models are not well suited for developmental and genetic studies of the cerebellum. The rapid transparent ex utero development in zebrafish allows direct access and precise visualization of all the major events in cerebellar development. The superficial position of the cerebellar primordium and cerebellum further facilitates in vivo imaging of cerebellar structures and developmental events at single cell resolution. Furthermore, zebrafish is amenable to high-throughput screening techniques and forward genetics because of its fecundity and easy keeping. Forward genetics screens in zebrafish have resulted in several isolated cerebellar mutants and substantially contributed to the understanding of the genetic networks involved in hindbrain development (Bae et al. 2009; Brand et al. 1996). Recent developments in genetic tools, including the use of site specific recombinases, efficient transgenesis, inducible gene expression systems, and the targeted genome lesioning technologies TALEN and Cas9/CRISPR has opened up new avenues to manipulate and edit the genome of zebrafish (Hans et al. 2009; Scott 2009; Housden et al. 2016; Li et al. 2016)}. These tools enable the use of genome-wide genetic approaches, such as enhancer/exon traps and cell specific temporal control of gene expression in zebrafish. Several seminal papers have used these technologies to successfully elucidate mechanisms involved in the morphogenesis, neurogenesis and cell migration in the cerebellum (Bae et al. 2009; Chaplin et al. ; Hans et al. 2009; Volkmann et al. ; Volkmann et al. 2008). In addition, the use of genetically encoded sensors and probes that allows detection and manipulation of neuronal activity using optical methods have open up new means to study the physiology and function of the cerebellum (Simmich et al. 2012; Matsui et al. 2014). Taken together, these features have allowed zebrafish to emerge as a complete model for studies of molecular, cellular and physiological mechanisms involved in cerebellar development and function at both cell and circuit level.