Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

  1. Miriam Bibel and
  2. Yves-Alain Barde1
  1. Department of Neurobiochemistry, Max-Planck Institute of Neurobiology, 82152 Planegg-Martinsried, Germany

This extract was created in the absence of an abstract.

Neurons are specialized cells with a complex morphology that represent the functional unit of the nervous system. They are generated in remarkable numbers, particularly in higher vertebrates. In the human brain, for example, there may be ∼85 billion neurons (Williams and Herrup 1988). There is little cell division in the adult nervous system of vertebrates, and in most areas, the final number of neurons is determined early in development, at about the time when neurons extend axons (Oppenheim 1991). Neuronal numbers are controlled both by cell-intrinsic and cell-extrinsic programs. Cell-intrinsic programs govern basic aspects of neuronal differentiation in vertebrates, and a number of transcription factors have been shown to be expressed in well-defined areas of the nervous system (for review, see Rubenstein et al. 1998). Cell-extrinsic mechanisms play a prominent role in vertebrates. They involve the secretion of diffusible molecules controlling the survival of neurons produced in excess early in development, a process thought to help match the size of neuronal populations with the territory they innervate (Purves 1988; Oppenheim 1991). However, much of the developmental growth of the animal must still take place by the time these numerical adjustments are completed (Purves 1988). The neurons that have escaped elimination grow proportionally with the organism, enlarging their size by adding dendrites that grow out from the cell bodies.

Secreted proteins play a crucial role in the control of neuronal numbers and of dendritic growth. The best studied group is a family of structurally related molecules termed neurotrophins (Barde 1990). The first neurotrophin identified was originally designated “the” nerve growth factor (NGF; Levi-Montalcini 1966). However, only very few neurons were found to be NGF responsive in the central nervous system (CNS), and the isolation of brain-derived neurotrophic factor (BDNF) from the brain helped establish the concept that the fate and …

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