The Critical Role of YAP/BMP/ID1 Axis on Simulated Microgravity-Induced Neural Tube Defects in Human Brain Organoids

Area of Science:

• Developmental Biology
• Neuroscience
• Space Biology

Background:

• Embryonic development relies on integrated biochemical and biophysical signals.
• Neural tube formation is crucial for central nervous system development.
• The impact of microgravity on neurodevelopment is not well understood.

Purpose of the Study:

• To investigate the effects of simulated microgravity (SMG) on human brain organoid development.
• To elucidate the molecular mechanisms underlying microgravity-induced neurodevelopmental defects.
• To identify potential countermeasures for space-related neurodevelopmental challenges.

Main Methods:

• Utilized human brain organoids to model early human brain development.
• Applied stimulated microgravity (SMG) to brain organoids.
• Performed bulk gene expression analysis and single-cell RNA sequencing.
• Investigated N-cadherin-based adherens junctions, Hippo and BMP signaling pathways, and neural stem/progenitor cell subpopulations.

Main Results:

• SMG impaired N-cadherin-based adherens junction formation, causing neural tube defects.
• SMG dysregulated neural stem cell self-renewal and neuroepithelial organization.
• Altered Hippo and BMP signaling pathways were observed, with rescue possible via YAP/BMP/ID1 axis regulation.
• SMG perturbed neural stem and progenitor cell subpopulations, affecting cell communication and proliferation.
• Neuropathological deficits were persistent even after return to normal gravity.

Conclusions:

• Simulated microgravity induces significant molecular and cellular abnormalities during human brain development.
• These findings highlight potential risks to neurodevelopment during space missions.
• The study provides a basis for developing countermeasures to mitigate microgravity's effects on the developing brain.