Neural Progenitors as a Novel Pathogenic Mechanism in Microcephaly
Reiner, O.; Tshuva, R. Y.; Bok, J.; Nonaka, M.; Xue, X.; Bhattacharya, B.; Kshirsagar, A.; Olender, T.; Danan-Gotthold, M.; Fu, J.; Sapir, T.
Show abstract
Despite their significance, the genetic and molecular bases of neurodevelopmental disorders remain poorly understood. In this study, using human brain organoids and mouse models, we show that loss of NDE1, a gene closely associated with microcephaly, disrupts progenitor identity, prolongs mitosis, and alters regional patterning in the forebrain. NDE1 knockout leads to a caudal identity shift of neural progenitor cells in the organoids and mouse brains, coinciding with aberrant ERK signaling. Notably, downstream activation of the ERK pathway restored rostral PAX6 expression in human brain organoids. Parallel analyses of Nde1 knockout mice confirmed disrupted regional patterning of the forebrain. Together, our data establish NDE1 as a critical regulator of early human brain regionalization and elucidate molecular mechanisms underlying the structural abnormalities observed in NDE1-associated microcephaly.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- CTNND2 regulation by the SRGAP2 protein family links human evolution to synaptic neoteny 96%
- Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates 96%
- Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline 96%
Similar papers in this journal
- Integrated single-cell transcriptomic and epigenetic analyses of cell-state transition and lineage commitment in the embryonic mouse cerebellum 97%
- A telencephalon cell type atlas for goldfish reveals diversity in the evolution of spatial structure and cell types 96%
- Tissue-wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression 96%
Similar papers in this journal
- A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro 98%
- Intrinsic microtubule destabilization of multiciliated choroid plexus epithelial cells during postnatal lifetime 96%
- In vivo functional genomics identifies essentiality of potassium homeostasis in medulloblastoma 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.