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The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), and NT4/5 are all found in the developing cerebellum. Granule cells, the major target neurons of mossy fibers, express BDNF during mossy fiber synaptogenesis. To determine whether neurotrophins contribute to the development of cerebellar afferent axons, we characterized the effects of neurotrophins on the growth of mossy fiber neurons from mice and rats in vitro. For a mossy fiber source, we used the basilar pontine nuclei (BPN), the major source of cerebellar mossy fibers in mammals. BDNF and NT4/5 increased BPN neuron survival, neurite outgrowth, growth cone size, and elongation rate, while neither NT3 nor NGF increased survival or outgrowth. In addition, BDNF and NT4/5 reduced the size of neurite bundles. Consistent with these effects, in situ hybridization on cultured basilar pontine neurons revealed the presence of mRNA encoding the TrkB receptor which binds both BDNF and NT4/5 with high affinity. We detected little or no message encoding the TrkC receptor which preferentially binds NT3. BDNF and NT4/5 also increased TrkB mRNA levels in BPN neurons. In addition to previously established functions as an autocrine/paracrine trophic factor for granule cells, the present results indicate that cerebellar BDNF may also act as a target-derived trophic factor for basilar pontine mossy fibers. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 254–269, 1999

In a search for determinants of positional information in the embryonic eye, we isolated two monoclonal anti bodies that label strongly the dorsal part of the undifferentiated embryonic retina in mammals, bird and cold blooded vertebrates. In the chick, the optic tectum is labeled in a corresponding fashion, the ventral tectum more heavily than the dorsal tectum. Through biochemical and molecular analysis both antibodies were found to recognize a protein that has been cloned repeatedly, first in a screen with antibodies to the ‘68K-laminin receptor’ (Wewer et al. (1986)Cancer Res. 47, 5691–5698), a name that may not exhaustively describe its function. Western blots show the protein to be present in most or all tissues, and Western and Southern blots reveal a high degree of conservation in the detected signals up to invertebrates and bacteria. Despite the very strong and selective labeling of the dorsal retina in conventional immunohistochemical preparations, the protein and its mRNA are present in even amounts throughout the embryonic retina, as demonstrated by Western and Northern blots of bisected retinas, and immunohistochemically in retinas fixed with ethylene glycole bissuccinimide (EGS), an NH2-group crosslinker with very long spacer arm. This indicates that the dorsoventral asymmetry in the embryonic retina is not in the amount but in the configuration of this protein; whether this difference relates to laminin binding is not known.