Related Experiment Video

Updated: Aug 24, 2026

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
10:25

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

Published on: December 12, 2019

Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway

Xudong Yang1, Rüdiger Klein, Xiaolin Tian

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Developmental Biology
|April 15, 2004
PubMed

Insights

Notch signaling regulates neural progenitor apoptosis during development. Activating Notch1 increases cell death, while blocking it reduces apoptosis, highlighting its role in neural development.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Notch signaling is crucial for cell-fate determination in developing organisms.
  • Its specific role in neural progenitor apoptosis remains incompletely understood.

Purpose of the Study:

  • To investigate the role of Notch signaling in regulating apoptotic cell death of neural progenitor cells.
  • To elucidate the molecular mechanisms by which Notch signaling influences neural progenitor survival.

Main Methods:

  • Generation and analysis of cell type-specific conditional transgenic and knockout mice for Notch1 and Presenilin-1.
  • Assessment of apoptosis levels in neural progenitor cells under varying Notch signaling conditions.
  • Analysis of p53 pathway activation and target gene expression (Bax, Noxa) following Notch activation.

Main Results:

  • Conditional activation of Notch1 in early neural progenitors induces significant apoptosis, reducing the progenitor pool.
  • Attenuation of Notch signaling via conditional knockout or Presenilin-1 deficiency decreases neural progenitor apoptosis.
  • Notch activation elevates nuclear p53 and upregulates Bax and Noxa, with p53 deficiency suppressing Notch-induced apoptosis.

Conclusions:

  • Notch signaling plays a significant role in promoting apoptotic cell death of neural progenitor cells during early mammalian development.
  • The p53 pathway is a critical mediator of Notch-induced apoptosis in neural progenitors.
  • These findings reveal a novel function of Notch signaling in regulating neural development through apoptosis control.

More Related Videos

Stimulation of Notch Signaling in Mouse Osteoclast Precursors08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress09:51

Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress

Published on: May 7, 2014

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.