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Related Concept Videos

Neurulation01:30

Neurulation

42.5K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
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Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders
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Neural Progenitors as a Novel Pathogenic Mechanism in Microcephaly.

Rami Yair Tshuva, Jeyoon Bok, Mio Nonaka

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    Loss of the NDE1 gene impairs early brain development, causing microcephaly by disrupting progenitor cells and forebrain regionalization. Restoring ERK signaling partially corrected these developmental defects.

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    Area of Science:

    • Neuroscience
    • Developmental Biology
    • Genetics

    Background:

    • Neurodevelopmental disorders, including microcephaly, have poorly understood genetic and molecular underpinnings.
    • The gene NDE1 is associated with microcephaly, but its precise role in brain development is unclear.

    Purpose of the Study:

    • To investigate the function of NDE1 in human brain development using organoids and mouse models.
    • To elucidate the molecular mechanisms by which NDE1 loss leads to microcephaly and forebrain abnormalities.

    Main Methods:

    • Utilized human brain organoids and NDE1 knockout mouse models.
    • Analyzed progenitor cell identity, mitosis duration, and regional patterning.
    • Investigated the role of ERK signaling pathway.

    Main Results:

    • NDE1 loss disrupted progenitor identity and prolonged mitosis in human brain organoids and mouse models.
    • NDE1 knockout caused a caudal shift in neural progenitor cell identity and altered forebrain regional patterning.
    • Aberrant ERK signaling was observed in NDE1 knockout models, and its downstream activation partially restored rostral PAX6 expression.

    Conclusions:

    • NDE1 is a critical regulator of early human brain regionalization.
    • Disruption of NDE1 function leads to structural abnormalities in microcephaly through mechanisms involving progenitor cell identity and ERK signaling.