Related Experiment Video

Updated: Aug 20, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK

Catherine Barthélémy1, Christopher E Henderson, Brigitte Pettmann

  • 1UMR 623, Developmental Biology Institute of Marseille, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de la Méditerranée, Marseille, France. barthelemy@ibdm.univ-mrs.fr

BMC Neuroscience
|December 1, 2004
PubMed
Abstract

Insights

Neurotrophic factors regulate motoneuron survival by controlling FOXO3a nuclear translocation and FasL expression. This pathway, involving JNK signaling, is crucial for programmed cell death in developing spinal cord motoneurons.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Death Research

Background:

  • Programmed cell death in developing spinal cord motoneurons is linked to neurotrophic factor availability.
  • Trophic factor deprivation in motoneurons leads to increased FasL expression, activating a cell death pathway.
  • The precise regulation of FasL by trophic factors remains unclear, though FOXO3a and JNK are implicated in other cell types.

Purpose of the Study:

  • To investigate the role of FOXO3a and JNK in regulating FasL expression and programmed cell death in developing spinal cord motoneurons.
  • To elucidate the mechanism by which neurotrophic factors control motoneuron survival via the Fas/FasL pathway.

Main Methods:

  • In vitro studies using embryonic spinal motoneurons.
  • Analysis of Foxo3a translocation in response to neurotrophic factor withdrawal.
  • Assessment of cell death in Fas and FasL mutant motoneurons.
  • Evaluation of JNK inhibitors' effects on motoneuron death.

Main Results:

  • Removal of neurotrophic factors and reduced PI3K/Akt signaling cause Foxo3a to move to the nucleus, initiating cell death.
  • Cell death is significantly reduced in motoneurons lacking functional Fas or FasL.
  • Inhibition of JNK signaling decreases motoneuron death, indicating a crucial role for JNK in activating the Fas/FasL pathway.

Conclusions:

  • FOXO transcriptional regulators link signaling pathways to the cell death machinery in motoneurons.
  • The FOXO3a-JNK-Fas/FasL axis is a key regulator of programmed cell death in developing spinal cord motoneurons.
  • This study clarifies a critical mechanism governing motoneuron survival during development.

Related Concept Videos

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...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...