Using cortical organoids to understand the pathogenesis of malformations of cortical development
Malformations of cortical development encompass a broad range of disorders associated with abnormalities in corticogenesis. Widespread abnormalities in neuronal formation or migration can lead to small head size or microcephaly with disorganized placement of cell types. Specific, localized malformat...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1522652/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841527805072900096 |
|---|---|
| author | Kellen D. Winden Isabel Gisser Mustafa Sahin |
| author_facet | Kellen D. Winden Isabel Gisser Mustafa Sahin |
| author_sort | Kellen D. Winden |
| collection | DOAJ |
| description | Malformations of cortical development encompass a broad range of disorders associated with abnormalities in corticogenesis. Widespread abnormalities in neuronal formation or migration can lead to small head size or microcephaly with disorganized placement of cell types. Specific, localized malformations are termed focal cortical dysplasias (FCD). Neurodevelopmental disorders are common in all types of malformations of cortical development with the most prominent being refractory epilepsy, behavioral disorders such as autism spectrum disorder (ASD), and learning disorders. Several genetic pathways have been associated with these disorders from control of cell cycle and cytoskeletal dynamics in global malformations to variants in growth factor signaling pathways, especially those interacting with the mechanistic target of rapamycin (mTOR), in FCDs. Despite advances in understanding these disorders, the underlying developmental pathways that lead to lesion formation and mechanisms through which defects in cortical development cause specific neurological symptoms often remains unclear. One limitation is the difficulty in modeling these disorders, as animal models frequently do not faithfully mirror the human phenotype. To circumvent this obstacle, many investigators have turned to three-dimensional human stem cell models of the brain, known as organoids, because they recapitulate early neurodevelopmental processes. High throughput analysis of these organoids presents a promising opportunity to model pathophysiological processes across the breadth of malformations of cortical development. In this review, we highlight advances in understanding the pathophysiology of brain malformations using organoid models. |
| format | Article |
| id | doaj-art-1ad3460b79c94a20893ae4d81f7ffed6 |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-1ad3460b79c94a20893ae4d81f7ffed62025-01-15T06:10:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-01-011810.3389/fnins.2024.15226521522652Using cortical organoids to understand the pathogenesis of malformations of cortical developmentKellen D. WindenIsabel GisserMustafa SahinMalformations of cortical development encompass a broad range of disorders associated with abnormalities in corticogenesis. Widespread abnormalities in neuronal formation or migration can lead to small head size or microcephaly with disorganized placement of cell types. Specific, localized malformations are termed focal cortical dysplasias (FCD). Neurodevelopmental disorders are common in all types of malformations of cortical development with the most prominent being refractory epilepsy, behavioral disorders such as autism spectrum disorder (ASD), and learning disorders. Several genetic pathways have been associated with these disorders from control of cell cycle and cytoskeletal dynamics in global malformations to variants in growth factor signaling pathways, especially those interacting with the mechanistic target of rapamycin (mTOR), in FCDs. Despite advances in understanding these disorders, the underlying developmental pathways that lead to lesion formation and mechanisms through which defects in cortical development cause specific neurological symptoms often remains unclear. One limitation is the difficulty in modeling these disorders, as animal models frequently do not faithfully mirror the human phenotype. To circumvent this obstacle, many investigators have turned to three-dimensional human stem cell models of the brain, known as organoids, because they recapitulate early neurodevelopmental processes. High throughput analysis of these organoids presents a promising opportunity to model pathophysiological processes across the breadth of malformations of cortical development. In this review, we highlight advances in understanding the pathophysiology of brain malformations using organoid models.https://www.frontiersin.org/articles/10.3389/fnins.2024.1522652/fullASDtuberous sclerosisPTEN hamartoma tumor syndromeiPSCscortical organoidsmTOR |
| spellingShingle | Kellen D. Winden Isabel Gisser Mustafa Sahin Using cortical organoids to understand the pathogenesis of malformations of cortical development Frontiers in Neuroscience ASD tuberous sclerosis PTEN hamartoma tumor syndrome iPSCs cortical organoids mTOR |
| title | Using cortical organoids to understand the pathogenesis of malformations of cortical development |
| title_full | Using cortical organoids to understand the pathogenesis of malformations of cortical development |
| title_fullStr | Using cortical organoids to understand the pathogenesis of malformations of cortical development |
| title_full_unstemmed | Using cortical organoids to understand the pathogenesis of malformations of cortical development |
| title_short | Using cortical organoids to understand the pathogenesis of malformations of cortical development |
| title_sort | using cortical organoids to understand the pathogenesis of malformations of cortical development |
| topic | ASD tuberous sclerosis PTEN hamartoma tumor syndrome iPSCs cortical organoids mTOR |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1522652/full |
| work_keys_str_mv | AT kellendwinden usingcorticalorganoidstounderstandthepathogenesisofmalformationsofcorticaldevelopment AT isabelgisser usingcorticalorganoidstounderstandthepathogenesisofmalformationsofcorticaldevelopment AT mustafasahin usingcorticalorganoidstounderstandthepathogenesisofmalformationsofcorticaldevelopment |