Publications by authors named "Melanie Einsiedler"
Disorders of neuronal mispositioning during brain development are phenotypically heterogeneous and their genetic causes remain largely unknown. Here, we report biallelic variants in a Hippo signaling factor--in a patient with one such disorder, periventricular nodular heterotopia (PH). Genetic and cellular analysis of both variants confirmed them to be loss-of-function with enhanced sensitivity to transcript degradation via nonsense mediated decay (NMD) or increased protein turnover via the proteasome.
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- The development of the cerebral cortex relies on the proper growth and differentiation of neural stem cells, and mistakes in these processes can lead to issues like periventricular neuronal heterotopia, where neurons are misplaced.
- Mutations in the genes DCHS1 and FAT4 have been identified as causing a genetic syndrome in humans that includes this mislocalization of neurons.
- In experiments with mice, reducing the expression of Dchs1 or Fat4 led to an increase in neural progenitor cells and a decrease in their conversion to neurons, resulting in similar brain structure abnormalities seen in humans, which could be reversed by reducing Yap activity, highlighting its role in neurogenesis regulation. *