Using human brain organoids and mouse models, it is shown that loss of NDE1, a gene closely associated with microcephaly, disrupts progenitor identity, prolongs mitosis, and alters regional patterning in the forebrain.
Abstract
Despite their signi fi cance, 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 con fi rmed 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 -asso- ciated microcephaly.
It is demonstrated that Menin, encoded by the multiple endocrine neoplasia type 1 (Men1) gene, is essential for neurogenesis, providing insight into the formation of the cerebral cortex.
Shu-Zhong Wang, Kai Zhuang, Liu-Rong Chen et al.· Cell Reports· 0 citations
It is indicated that bobby sox homolog (BBX) maintains normal cortical development by restraining the p53-p21-RB axis, thereby preventing premature cell-cycle exit and senescence in developing neural cells.
Y. Yoon, Gwang Yeong Kim, Woo-Young Lim et al.· EMBO Reports· 0 citations
Aging is accompanied by complex alterations in brain structure and functions, with growing evidence implicating the choroid plexus (CP) as a key regulator of cognitive and motor function. Here, we investigated age-related changes in the CP of the gray mouse lemur (Microcebus murinus), a non-human primate model that rec...
F. Amiot, Antxon Etchebest, B. Andriambelo et al.· PLoS ONE· 0 citations
A major challenge in precision medicine is to understand the cellular origin of disease-causing genetic alterations. One prominent example is the Negr1 locus, where common non-coding variants are associated with an unusually broad range of human traits and conditions, including body mass index (BMI), major depression,...
Andrés González-Suarez, Laura Pola-Morell, Hernán López-Schier· bioRxiv· 0 citations
It is shown that Fragile X autosomal homolog 1 (FXR1), a brain-enriched RNA-binding protein (RBP), is essential for human neurogenesis, and post-transcriptional regulation is established as a key mechanism that maintains neurogenic potency of human NPCs.
Natasha M. Méndez-Albelo, Ya-Jie Zhang, Soraya O. Sandoval et al.· Stem Cell Reports· 0 citations
The results demonstrate that EPM1 COs display increased electrophysiological activity and disrupted excitatory/inhibitory (E/I) balance, and identify the CSTB-SHH-EV axis as a potential therapeutic target for mitigating the E/I imbalance associated with EPM1.
Andrea Forero, V. Pravata, Fabrizia Pipicelli et al.· Science Advances· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
