Requirement of neurotrophin-3 for the survival of proliferating trigeminal ganglion progenitor cells.

The aim of this study was to identify the physiological role of neurotrophin-3 (NT-3) in the development of trigeminal ganglion sensory neurons. For this purpose we have analysed mice carrying a deletion in the NT-3 gene (NT-3-/- mice). In these mice, by embryonic day (E) 11.25% of the trigeminal ganglion neurons were absent and one day later, approximately 50% were absent, after which no further significant changes were observed. Mice carrying one functional NT-3 gene (NT-3+/- mice) displayed a less severe deficit than that of NT-3-/- mice. Whereas programmed cell death occurred between E12 and E14 in the control mice, pronounced excessive cell death was apparent prior to this in the NT-3-/- mice. The excessive cell death led to a progressive decline in the number of proliferating cells without a significant change in the fraction of dividing cells and total number of neurons, indicating that the neuronal deficit of NT-3-/- mice was caused by cell death of trigeminal ganglion progenitors. Furthermore, the degenerating cells had incorporated BrdU, a nucleotide analogue which labels proliferating cells, and expressed nestin, a marker for progenitor cells. Only rarely were degenerating cells seen to express peripherin, present in postmitotic neurons. These data provide evidence that NT-3 is a survival factor for trigeminal ganglion progenitor cells, and suggests that limiting amounts of NT-3 could influence progenitor cell numbers during gangliogenesis.