Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia
| العنوان: | Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia |
|---|---|
| المؤلفون: | Mariana Schroeder, Johannes Klaus, Stephen P. Robertson, Silvia Cappello, Malgorzata Santel, Micha Drukker, Christina Kyrousi, Rossella Di Giaimo, Barbara Treutlein, J. Gray Camp, Adam C. O’Neill, Chiara Tocco, Ane Cristina Ayo-Martin, Ejona Rusha, Stephan Riesenberg, Sabina Kanton, Magdalena Götz |
| المساهمون: | Klaus, J., Kanton, S., Kyrousi, C., Ayo-Martin, A. C., Di Giaimo, R., Riesenberg, S., O'Neill, A. C., Camp, J. G., Tocco, C., Santel, M., Rusha, E., Drukker, M., Schroeder, M., Gotz, M., Robertson, S. P., Treutlein, B., Cappello, S. |
| المصدر: | Nature Medicine, 25 Nature Medicine |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Organoid, 0301 basic medicine, Biology, Time-Lapse Imaging, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Periventricular Nodular Heterotopia, Cell Movement, Progenitor cell, Induced pluripotent stem cell, Cerebrum, Tumor Suppressor Protein, DCHS1, Sequence Analysis, RNA, Cadherin, Infant, Newborn, General Medicine, Neuron, Phenotype, Neural stem cell, 3. Good health, Cell biology, Single-Cell Analysi, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Axon guidance, Human |
| الوصف: | Malformations of the human cortex represent a major cause of disability1. Mouse models with mutations in known causal genes only partially recapitulate the phenotypes and are therefore not unlimitedly suited for understanding the molecular and cellular mechanisms responsible for these conditions(2). Here we study periventricular heterotopia (PH) by analyzing cerebral organoids derived from induced pluripotent stem cells (iPSCs) of patients with mutations in the cadherin receptor-ligand pair DCHS1 and FAT4 or from isogenic knockout (KO) lines(1,3). Our results show that human cerebral organoids reproduce the cortical heterotopia associated with PH. Mutations in DCHS1 and FAT4 or knockdown of their expression causes changes in the morphology of neural progenitor cells and result in defective neuronal migration dynamics only in a subset of neurons. Single-cell RNA-sequencing (scRNA-seq) data reveal a subpopulation of mutant neurons with dysregulated genes involved in axon guidance, neuronal migration and patterning. We suggest that defective neural progenitor cell (NPC) morphology and an altered navigation system in a subset of neurons underlie this form of PH. |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e13544b3b6e8d5f033c45744e8bf4cfTest https://doi.org/10.1038/s41591-019-0371-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2e13544b3b6e8d5f033c45744e8bf4cf |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |