REGULATION OF NEUROTROPHIN RECEPTORS DURING THE MATURATION OF THE MAMMALIAN VISUAL-SYSTEM

Cell division, cell death, and remodeling of connections are major fea tures of the construction of the mammalian CNS. We have begun to addre ss the role of neurotrophins in these events through characterization of the expression of their receptors in the developing ferret visual s ystem. By use of chemical cross-linking of iodinated neurotrophins, pr oteins corresponding to trkB, trkC, and p75 were identified as recepto rs for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT -3) throughout development. BDNF was also cross-linked to a truncated form of trkB that lacks the tyrosine kinase domain (trkB.T 1) in retin al target tissues and in cortex. At the earliest developmental age exa mined (E24), the ratio of full-length to truncated trkB is much greate r than 1 in the retinal target tissues, LGN and superior colliculus. D uring the ensuing period of retinal ganglion cell death and segregatio n into eye-specific layers, the amount of truncated trkB increases mar kedly relative to full-length trkB. By P27, truncated trkB is the pred ominant receptor for BDNF in the retinal target tissues and this patte rn is maintained into adulthood. Within all subdivisions of visual cor tex including the ventricular zone (VZ), intermediate zone (IZ), and c ortical plate (CP), similar profiles of bands are observed. The develo pmental increase in abundance of truncated trkB relative to full-lengt h occurs earliest in the VZ, with a major increase between E30 and P3. In the IZ, this shift to a predominance of truncated trkB occurs betw een P15 and P30, while in the CP the shift is even further delayed, no t occurring until after P30. Within each subdivision of cortex, the sh ift to a predominance of truncated trkB occurs at times that correlate with the onset of cell death and maturation of axonal connections. Th is study demonstrates that members of the trk family, previously ident ified in the CNS on the basis of mRNA transcripts, are present as rece ptors with specific binding affinities for BDNF and NT-3. Moreover, th e correspondence between the developmental shift from full-length to t runcated trkB and the critical periods for cell fate determination, ce ll death, and axonal remodeling suggests an important role for neurotr ophic factors in the development of the visual system.