Neural precursor cell survival

Apart from the cell survival effects, BDNF appears to have a role in the maturation of sensory neurons from neural precursor cells. In cultures of neural crest cells, the addition of BDNF leads to an increase in the number of sensory neurons (Sieber-Blum, 1991). This is not due to an increase in the total number of cells but to a corresponding decrease in the proportion of undifferentiated cells. Likewise, in cultures of early sensory neurons that are not yet neurotrophin responsive, the addition of BDNF causes an acceleration of their maturation (Wright et al, 1992). Thus, BDNF may be involved with cell differentiation at early stages of development and with cell survival at later stages. 

Mukhida K, Baghbaderani BA, Hong M, Lewington M, Phillips T, McLeod M, Sen A, Behie LA, Mendez I. 2008. Survival, differentiation, and migration ofbioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats. Neurosurgical Focus 24(3-4) E8. 

If these findings are taken together, then a sequence of steps from neural crest precursor cell to mature sensory neuron can be proposed, each driven by a different factor. The first step, from precursor cell to immature neuron, requires LIF. The second step, from immature neuron to factor-dependent immature neuron, requires (or is stimulated by) BDNF or NT-3 the third step, the survival of the factor-dependent neuron during target innervation and further maturation, requires NGF. 

These experiments were the first to demonstrate that the development of a presumably committed population of neural crest cells can be directly manipulated by culture conditions. The continued proliferation of the cells under one set of conditions indicates that the precursors can still divide, and the observation that they will all differentiate into ChAT-positive neuron-like cells suggests that they are indeed neuronal precursor cells. The conditions used to stimulate the differentiation of the cells are the same which promote the survival and/or cholinergic development of ciliary ganglion neurons. This reinforces the idea that the subpopulation of neural crest cells used in this study represents ciliary neuron precursors (Barald,... 

Other functions of NT-3 early in development include induction of proliferation and differentiation of neural crest progenitor cells (Kalcheim et al., 1992, Chalazonitis et al., 1994), maintain survival of proliferating sympathetic neuroblasts and peripheral sensory neurons (Birren et al., 1993 DiCicco-Bloom et al., 1993 Gaese et al., 1994), promote survival and proliferation of oligodendrocyte precursors (Barres et al., 1993), and regulate the differentiation of sympathetic neuroblasts (Verdi and Anderson, 1994) (Fig. 1). 

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