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Regulation of neuronal survival and death by extracellular signals during development
1Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, Summerhall Square, Edinburgh EH9 1QH, UK. Alun.Davies@ed.ac.uk
Abstract:
Cell death is a prominent feature of the developing vertebrate nervous system, affecting neurons, glial cells and their progenitors. The most extensively studied and best understood phase of cell death occurs in populations of neurons shortly after they begin establishing connections with other neurons and/or non-neural tissues. This phase of cell death makes appropriate adjustments to the relative sizes of interconnected groups of neurons and matches the size of neuronal populations that innervate non-neural tissues to the optimal requirements of these tissues. The fate of neurons during this period of development is regulated by a variety of secreted proteins that either promote survival or bring about cell death after binding to receptors expressed on the neurons. These proteins may be derived from the targets the neurons innervate, the afferents they receive or from associated glial cells, or they may be secreted by the neurons themselves. In this review, I will outline the established and emerging principles that modulate neuronal number in the developing nervous system.
Insights
Neuronal cell death is crucial for vertebrate nervous system development, ensuring proper connections and tissue innervation. Secreted proteins regulate neuron survival and death, optimizing neural circuit formation.
Area of Science:
- Neuroscience
- Developmental Biology
Background:
- Cell death is a significant aspect of vertebrate nervous system development.
- Neuronal cell death is particularly studied during the establishment of neural connections.
Purpose of the Study:
- To review established and emerging principles governing neuronal number modulation in the developing nervous system.
Main Methods:
- This review synthesizes existing research on neuronal cell death.
- Focuses on secreted proteins and their receptors regulating neuronal fate.
Main Results:
- Cell death refines neuronal populations after connection establishment.
- Ensures optimal matching of neuronal numbers to target tissue requirements.
- Secreted proteins from various sources (targets, afferents, glia, neurons) regulate survival and death.
Conclusions:
- Neuronal number regulation via programmed cell death is essential for nervous system development.
- Understanding these molecular mechanisms is key to comprehending neural circuit formation.