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Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture

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Abstract

Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left–right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left–right differentiation are an important factor in the ontogenesis of functional lateralization.

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Acknowledgments

This study was supported by a Grant from the Deutsche Forschungsgemeinschaft BE4045/10-1 and 10-2 to C.B.

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Correspondence to Christian Beste.

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C. Beste and S. Ocklenburg contributed equally.

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Beste, C., Ocklenburg, S., von der Hagen, M. et al. Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture. Brain Struct Funct 221, 2487–2491 (2016). https://doi.org/10.1007/s00429-015-1051-6

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  • DOI: https://doi.org/10.1007/s00429-015-1051-6

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