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Journal of Neuroscience, Vol 14, 1795-1811, Copyright © 1994 by Society for Neuroscience
Regulation of neurotrophin receptors during the maturation of the mammalian visual system
KL Allendoerfer, RJ Cabelli, E Escandon, DR Kaplan, K Nikolics and CJ Shatz
Department of Molecular and Cell Biology, University of California at Berkeley 94720.
Cell division, cell death, and remodeling of connections are major features
of the construction of the mammalian CNS. We have begun to address the role
of neurotrophins in these events through characterization of the expression
of their receptors in the developing ferret visual system. By use of
chemical cross-linking of iodinated neurotrophins, proteins corresponding
to trkB, trkC, and p75 were identified as receptors 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. T1) in retinal target tissues and
in cortex. At the earliest developmental age examined (E24), the ratio of
full-length to truncated trkB is > > 1 in the retinal target tissues,
LGN and superior colliculus. During the ensuing period of retinal ganglion
cell death and segregation into eye-specific layers, the amount of
truncated trkB increases markedly relative to full-length trkB. By P27,
truncated trkB is the predominant receptor for BDNF in the retinal target
tissues and this pattern is maintained into adulthood. Within all
subdivisions of visual cortex including the ventricular zone (VZ),
intermediate zone (IZ), and cortical plate (CP), similar profiles of bands
are observed. The developmental increase in abundance of truncated trkB
relative to full-length 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 between P15 and P30, while in the CP the shift is even further
delayed, not occurring until after P30. Within each subdivision of cortex,
the shift to a predominance of truncated trkB occurs at times that
correlate with the onset of cell death and maturation of axonal
connections. This study demonstrates that members of the trk family,
previously identified in the CNS on the basis of mRNA transcripts, are
present as receptors with specific binding affinities for BDNF and NT- 3.
Moreover, the correspondence between the developmental shift from
full-length to truncated trkB and the critical periods for cell fate
determination, cell death, and axonal remodeling suggests an important role
for neurotrophic factors in the development of the visual system.
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