Cadherin-13 deficiency impacts murine serotonergic circuitries and cognitive function

Cadherin-13 (CDH13) is a member of the cadherin superfamily, which consists of cell-adhesion molecules. CDH13 is involved in the regulation of synapse formation and maintenance, as well as serotonergic neuron development. Serotonergic neurons mainly originate from the raphe nuclei in the hindbrain. In mice, CDH13 is first detected roughly halfway through the embryonic development in the hindbrain. Studies suggest a role of CDH13 in the pathophysiology of neurodevelopmental disorders. After previously investigating the role of CDH13 during embryonic development, we now aimed for the analysis of postnatal development. Postnatal development of serotonergic fiber density was investigated in the prefrontal cortex (PFC) of postnatal day 7 (P7) and P14 mice, using a conditional knockout model of Cdh13 in serotonergic neurons. Alongside this, gene expression of synaptic plasticity markers was investigated at P7. Our results show that the density of serotonergic fiber innervation in the PFC was higher in the conditional knockout (KO) model, compared to wildtype (WT) animals at P7, but not at P14, suggesting an influence of CDH13 on early postnatal development of serotonergic neurons. The effects of CDH13 influence are replaced or covered by other influencing factors between P7 and P14. Additionally, we found significantly lower gene expression of a plasticity marker in conditional KO mice compared to WT mice, hinting towards a possible influence of CDH13 on synaptic plasticity.