Summary: The FGF signaling pathway is an important extracellular regulator in the fate of neural stem cells switching from neurons to astrocytes in the cerebral cortex.
Source: Kanazawa University
Neurons and astrocytes are prominent cell types in the cerebral cortex. Neurons are the primary information processing cells in the brain, whereas astrocytes support and modulate their functions. For the sound functioning of the brain, it is crucial that proper numbers of neurons and astrocytes are generated during fetal brain development. The brain could not function correctly if only neurons or astrocytes were generated.
During fetal brain development, both neurons and astrocytes are generated from neural stem cells, which give rise to almost all cells in the cerebral cortex. One of the characteristics of this developmental process is that neural stem cells first generate neurons and, after that, start generating astrocytes. The “switch” to change the cell differentiation fate of neural stem cells from neurons to astrocytes has attracted much attention since the cell fate switch is key to the generation of proper numbers of neurons and astrocytes. However, it remained largely unknown.
The research group at Kanazawa University show that the switch determining the fate of two types of cells in the cerebral cortex generated from neural stem cells is based on the FGF signaling pathway. More specifically, it was found that enhancement of FGF signaling by introducing FGF in the cerebral cortex caused cells destined to become neurons to be differentiated into astrocytes. On the other hand, suppression of FGF signaling caused cells destined to become astrocytes to be differentiated into neurons. The present study has thus elucidated the mechanism responsible for determining the correct numbers of neurons and astrocytes during development of the fetal brain.
The research group has discovered the switch that determines the fate of cells in the developing cerebral cortex generated from neural stem cells, i.e. neurons and astrocytes; this switch involves the FGF signaling pathway. This may be relevant for understanding the pathology of brain disorders caused by unbalanced numbers of neurons and astrocytes by determining which disorders are based on abnormal FGF signaling.
About this neuroscience research article
Source: Kanazawa University Media Contacts: Yuki Kashin – Kanazawa University Image Source: The image is credited to Kanazawa University.
FGF signaling directs the cell fate switch from neurons to astrocytes in the developing mouse cerebral cortex
During mammalian neocortical development, neural precursor cells generate neurons first and astrocytes later. The cell fate switch from neurons to astrocytes is a key process generating proper numbers of neurons and astrocytes. Although the intracellular mechanisms regulating this cell fate switch have been well characterized, extracellular regulators are still largely unknown. Here, we uncovered that FGF regulates the cell fate switch from neurons to astrocytes in the developing cerebral cortex using mice of both sexes. We found that the FGF signaling pathway is activated in radial glial cells (RGCs) of the ventricular zone (VZ) at time points corresponding to the switch in cell fate. Our loss- and gain-of-function studies using in utero electroporation indicate that activation of FGF signaling is necessary and sufficient to change cell fate from neurons to astrocytes. We further found that the FGF-induced neuron-astrocyte cell fate switch is mediated by the MAPK pathway. These results indicate that FGF is a critical extracellular regulator of the cell fate switch from neurons to astrocytes in the mammalian cerebral cortex.
Although the intracellular mechanisms regulating the neuron-astrocyte cell fate switch in the mammalian cerebral cortex during development have been well studied, their upstream extracellular regulators remain unknown. By using in utero electroporation, our study provides in vivo data showing that activation of FGF signaling is necessary and sufficient for changing cell fate from neurons to astrocytes. Manipulation of FGF signaling activity led to drastic changes in the numbers of neurons and astrocytes. These results indicate that FGF is a key extracellular regulator determining the numbers of neurons and astrocytes in the mammalian cerebral cortex, and is indispensable for the establishment of appropriate neural circuitry.