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

Di Guo,

Bin Yao, Wenwei Shao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, role microgravity in neurodevelopment its underlying molecular mechanisms remain unclear. In this study, effects stimulated (SMG) on human brain organoids are investigated. SMG impairs N-cadherin-based adherens junction formation, leading to defects associated with dysregulated self-renewal capacity neuroepithelial disorganization organoids. Bulk gene expression analyses reveal that alters Hippo BMP signaling The neuropathological deficits SMG-treated can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing-cell RNA sequencing data show results perturbations number function stem progenitor cell subpopulations. One these subpopulations senses cues transmits subpopulation responsible morphogenesis, ultimately affecting proliferating population. Finally, intervention leads persistent neurologic damage even after returning normal gravity conditions. Collectively, study reveals cellular abnormalities during development, providing opportunities countermeasures maintain space.

Language: Английский

Prickle2 regulates apical junction remodeling and tissue fluidity during vertebrate neurulation DOI
Miho Matsuda, Sergei Y. Sokol

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(4)

Published: Jan. 22, 2025

The process of folding the flat neuroectoderm into an elongated neural tube depends on tissue fluidity, a property that allows epithelial deformation while preserving integrity. Neural also requires planar cell polarity (PCP) pathway. Here, we report Prickle2 (Pk2), core PCP component, increases fluidity by promoting remodeling apical junctions (AJs) in Xenopus embryos. This Pk2 activity is mediated unique evolutionarily conserved Ser/Thr-rich region (STR) carboxyterminal half protein. Mechanistically, effects require Rac1 and are accompanied increased dynamics C-cadherin tricellular junctions, hotspots AJ remodeling. Notably, depletion leads to accumulation mediolaterally oriented cells neuroectoderm, whereas overexpression or Pk1 containing Pk2-derived STR promotes elongation along anteroposterior axis. We propose Pk2-dependent regulation contributes response extrinsic cues.

Language: Английский

Citations

0
E-cadherin tunes tissue mechanical behavior before and during morphogenetic tissue flows DOI
Xun Wang, Christian Cupo, Sassan Ostvar

et al.

Current Biology, Journal Year: 2024, Volume and Issue: 34(15), P. 3367 - 3379.e5

Published: July 15, 2024

Language: Английский

Citations

2
Molecular and morphogenetic features of neurulation DOI Creative Commons

N. M. Nevmerzhytska,

O. M. Grabovyi,

L. M. Yaremenko

et al.

Zaporozhye Medical Journal, Journal Year: 2024, Volume and Issue: 26(1), P. 72 - 77

Published: Feb. 5, 2024

Neurulation occurs by two different mechanisms, called primary and secondary neurulation. In humans, neurulation along most of the rostrocaudal axis embryo, while caudally, only in lower sacral coccygeal regions. Primary is responsible for a change neural plate shape, lateral edges which rise then converge at dorsal midline to merge into tube. Initially, tube, formed as result neurulation, open both ends through so-called rostral caudal neuropores. These neuropores connect inner part tube with environment (amniotic cavity) later (by end neurulation) are closed. During brain spinal cord up upper region (up level junction between S1 S2 vertebral bodies), however, this anatomical (sacral-coccygeal division cord, conus medullaris filum terminale) due elongation cavitation cell mass medulla, transforms Thus, main differences that folds invaginates body embryo separates from surface ectoderm, forming an underlying hollow Mesenchymal сlusters form dense undergoes mesenchymal-epithelial transition forms cavities empty during terminal cord. Conclusions. Understanding detailed molecular genetic mechanisms each stage relevant widespread congenital defects, perfect knowledge on aspect all possible factors potential influence it will help develop modern options influencing some them, probably, cause decrease defects.

Language: Английский

Citations

0
The Critical Role of YAP/BMP/ID1 Axis on Simulated Microgravity‐Induced Neural Tube Defects in Human Brain Organoids DOI Creative Commons

Di Guo,

Bin Yao, Wenwei Shao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, role microgravity in neurodevelopment its underlying molecular mechanisms remain unclear. In this study, effects stimulated (SMG) on human brain organoids are investigated. SMG impairs N-cadherin-based adherens junction formation, leading to defects associated with dysregulated self-renewal capacity neuroepithelial disorganization organoids. Bulk gene expression analyses reveal that alters Hippo BMP signaling The neuropathological deficits SMG-treated can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing-cell RNA sequencing data show results perturbations number function stem progenitor cell subpopulations. One these subpopulations senses cues transmits subpopulation responsible morphogenesis, ultimately affecting proliferating population. Finally, intervention leads persistent neurologic damage even after returning normal gravity conditions. Collectively, study reveals cellular abnormalities during development, providing opportunities countermeasures maintain space.

Language: Английский

Citations

0