@phdthesis{Ku2022,
  author    = {Ku, Hsing-Ping},
  title     = {Cadherin-13 Deficiency Impacts Murine Serotonergic Circuitries and Cognitive Functions},
  doi       = {10.25972/OPUS-25144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251446},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Cadherin-13 (CDH13) is a member of the cadherin superfamily that lacks the typical transmembrane domain for classical cadherins and is instead attached to the cell membrane with a GPI-anchor. Over the years, numerous genome-wide association (GWA) studies have identified CDH13 as a risk factor for neurodevelopmental disorders, including attention- deficit/hyperactivity disorder (ADHD) and autism spectrum disorder. Further evidence using cultured cells and animal models has shown that CDH13 plays important roles in cell migration, neurite outgrowth and synaptic function of the central nervous system. Research in our laboratory demonstrated that the CDH13 deficiency resulted in increased cell density of serotonergic neurons of the dorsal raphe (DR) in developing and mature mouse brains as well as serotonergic hyperinnervation in the developing prefrontal cortex, one of the target areas of DR serotonergic neurons. In this study, the role of CDH13 was further explored using constitutive and serotonergic system-specific CDH13-deficient mouse models. Within the adult DR structure, the increased density of DR serotonergic neurons was found to be topographically restricted to the ventral and lateral-wing, but not dorsal, clusters of DR. Furthermore, serotonergic hyperinnervation was observed in the target region of DR serotonergic projection neurons in the lateral wings. Unexpectedly, these alterations were not observed in postnatal day 14 brains of CDH13-deficient mice. Additionally, behavioral assessments revealed cognitive deficits in terms of compromised learning and memory ability as well as impulsive-like behaviors in CDH13-deficient mice, indicating that the absence of CDH13 in the serotonergic system alone was sufficient to impact cognitive functions and behavioral competency. Lastly, in order to examine the organization of serotonergic circuitries systematically and to tackle limitations of conventional immunofluorescence, a pipeline of the whole-mount immunostaining in combination with the iDISCO+ based rapid tissue clearing techniques was established. This will facilitate future research of brain neurotransmitter systems at circuitry and/or whole-brain levels and provide an excellent alternative for visualizing detailed and comprehensive information about a biological system in its original space. In summary, this study provided new evidence of CDH13's contribution to proper brain development and cognitive function in mice, thereby offering insights into further advancement of therapeutic approaches for neurodevelopmental disorders.},
  language  = {en}
}
@phdthesis{Bacmeister2018,
  author    = {Bacmeister, Lucas},
  title     = {Effect of Cadherin-13 inactivation on different GABAergic interneuron populations of the mouse hippocampus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172693},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Cadherin-13 (CDH13) is an atypical member of the cadherin superfamily, a group of membrane proteins mediating calcium-dependent cellular adhesion. Although CDH13 shows the classical extracellular cadherin structure, the typical transmembrane and cytoplasmic domains are absent. Instead, CDH13 is attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. These findings and many studies from different fields suggest that CDH13 also plays a role as a cellular receptor. Interestingly, many genome-wide association studies (GWAS) have found CDH13 as a risk gene for attention-deficit/hyperactivity disorder (ADHD) and other neurodevelopmental disorders. In previous work from our research group, strong expression of Cdh13 mRNA in interneurons of the hippocampal stratum oriens (SO) was detected. Therefore, double-immunofluorescence studies were used to evaluate the degree of co-expression of CDH13 with seven markers of GABAergic interneuron subtypes. For this purpose, murine brains were double stained against CDH13 and the respective marker and the degree of colocalization in the SO of the hippocampus was assessed. Based on the result of this immunofluorescence study, quantitative differences in interneuron subtypes of the SO between Cdh13 knockout (ko), heterozygote (het) and wildtype (wt) mice were investigated in this dissertation using stereological methods. In addition, genotype- dependent differences in the expression of genes involved in GABAergic and glutamatergic neurotransmission were analyzed by quantitative real-time PCR (qRT-PCR). Primers targeting different GABA receptor subunits, vesicular GABA and glutamate transporter, GABA synthesizing enzymes and their interaction partners were used for this purpose. The results of the stereological quantification of the interneuron subtypes show no significant differences in cell number, cell density or volume of the SO between Cdh13 ko, het and wt mice. On the other hand, qRT-PCR results indicate significant differences in the expression of tropomyosin-related kinase B gene (TrkB), which encodes the receptor of brain-derived neurotrophic factor (BDNF), a regulator of GABAergic neurons. This finding supports a role for CDH13 in the regulation of BDNF signaling in the hippocampus.},
  subject      = {Cadherine},
  language  = {en}
}