Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning.
Neurotrophins were initially identified as critical regulators of neuronal survival. However, these factors have many additional functions. In the developing cerebellum the roles of the neurotrophins BDNF and NT3 include a surprising effect on patterning, as revealed by changes in foliation in neurotrophin-deficient mice. Here we examine the potential role of p75NTR in cerebellar development and patterning. We show that p75NTR is expressed at highest levels in the region of the cerebellum where foliation is altered in BDNF and NT3 mutants. Although the cerebellar phenotype of p75NTR mutant animals is indistinguishable from wild type, mutation of p75NTR in BDNF heterozygotes results in defects in foliation and in Purkinje cell morphologic development. Taken together, these data suggest that p75NTR activity is critical for cerebellar development under pathologic circumstances where neurotrophin levels are reduced.
Carter
Alexandre R
AR
Department of Neurobiology, Harvard Medical School, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Berry
Erin M
EM
Segal
Rosalind A
RA
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D019521:Body Patterning / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics; D064026:Calbindins; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development* / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020933:Neurotrophin 3 / Q000172:deficiency / Q000235:genetics; D010641:Phenotype; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D064030:S100 Calcium Binding Protein G