title: Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development.
abstract: Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are associated with the physiology of the striatum and the loss of its normal functioning under pathological conditions. The role of BDNF and its downstream signaling in regulating the development of the striatum has not been fully investigated, however. Here we report that ablation of Bdnf in both the cortex and substantia nigra depletes BDNF in the striatum, and leads to impaired striatal development, severe motor deficits, and postnatal lethality. Furthermore, striatal-specific ablation of TrkB, the gene encoding the high-affinity receptor for BDNF, is sufficient to elicit an array of striatal developmental abnormalities, including decreased anatomical volume, smaller neuronal nucleus size, loss of dendritic spines, reduced enkephalin expression, diminished nigral dopaminergic projections, and severe deficits in striatal dopamine signaling through DARPP32. In addition, TrkB ablation in striatal neurons elicits a non-cell-autonomous reduction of tyrosine hydroxylase protein level in the axonal projections of substantia nigral dopaminergic neurons. Thus, our results establish an essential function for TrkB in regulating the development of striatal neurons.
authors.affiliation: Department of Developmental Biology and Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Daishi
authors.initials: D
authors.lastname: Yui
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Luikart
authors.forename: Renée M
authors.initials: RM
authors.lastname: McKay
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Li
authors.forename: John L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014446:Tyrosine 3-Monooxygenase; D020813:Receptor, trkB