Burbach, J. P. H. | Search bioRxiv

bioRxiv2023

CNTN4 modulates neural elongation through interplay with APP

The neuronal cell adhesion molecule contactin-4 (CNTN4) has been genetically linked to autism spectrum disorders (ASD) and other psychiatric disorders. The Cntn4-deficient mouse model has previously shown that CNTN4 has important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex have not yet been investigated. Using Nissl staining, immunohistochemistry and Golgi staining the motor cortex of Cntn4-/- mice was analysed for abnormalities. Interacting partners of CNTN4 were identified by immunoprecipitation and mass spectrometry. Further analysis of the interaction between CNTN4 and APP utilised knockout human cells generated via CRISPR-Cas9 gene editing. Our study newly identified reduced cortical thickness in the motor cortex of Cntn4-/- mice, but cortical cell migration and differentiation were unaffected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of neurons in the motor cortex. Furthermore, mass spectrometry analysis identified an interaction partner for CNTN4, and we confirmed an interaction between CNTN4 and APP. Knockout human cells of CNTN4 and/or APP revealed a relationship between CNTN4 and APP. This study demonstrates that CNTN4 contributes to cortical development, and that its binding and interplay with APP controls neural elongation. This is an important finding for understanding the function of APP, a target protein for Alzheimers disease. The binding between Cntn4 and APP, which is involved in neurodevelopment, is essential for healthy nerve outgrowth.

neuroscience↗

bioRxiv2019

FMRF Gene Expression In The Nervous System Of The Squid Doryteuthis pealei* Hatchling

FMRFamide is a neuropeptide that is widely distributed in invertebrates and known to be involved in many physiological functions. Previously we noted marked differences in expression of the fmrf gene in the stellate ganglion of Doryteuthis pealei* compared to the central nervous system. In this study we aimed to examen the brain systems of Doryteuthis pealei* for the presence and distribution of fmrf-expressing cells and fiber networks. Late squid embryos and hatchlings were examined by in situ hybridization and immunohistochemistry in whole mounts and tissue sections. All central lobes contained limited numbers of scattered neurons expressing fmrf, but the FMRFamide-containing fiber systems were abundant and extensive, mostly present in the neuropil of lobes. Main clusters of neurons were located in the magnocellular and chromatophore lobes of the posterior subesophageal mass (PSM), and in dorsal aspects of the basal lobe (BL). Dense FMRFamide-immunoreactive fibers were particularly seen in the optic lobe (OL), medial and posterior supraesophageal masses (MSM and SPM) often with a commissural organization. The data show that the central lobes of Doryteuthis pealei hatchlings have a matured FMRFamide system organized in a limited number of centers, but with widely distributed efferents. This suggests that FMRFamide neurons are already functionally engaged in the late embryo. The localization indicates that control of chromatophores and fin movement are amongst these functions.

neuroscience↗