Dendrite complexity of sympathetic neurons is controlled during postnatal development by BMP signaling.
Dendrite development is controlled by the interplay of intrinsic and extrinsic signals affecting initiation, growth, and maintenance of complex dendrites. Bone morphogenetic proteins (BMPs) stimulate dendrite growth in cultures of sympathetic, cortical, and hippocampal neurons but it was unclear whether BMPs control dendrite morphology in vivo. Using a conditional knock-out strategy to eliminate Bmpr1a and Smad4 in immature noradrenergic sympathetic neurons we now show that dendrite length, complexity, and neuron cell body size are reduced in adult mice deficient of Bmpr1a. The combined deletion of Bmpr1a and Bmpr1b causes no further decrease in dendritic features. Sympathetic neurons devoid of Bmpr1a/1b display normal Smad1/5/8 phosphorylation, which suggests that Smad-independent signaling paths are involved in dendritic growth control downstream of BMPR1A/B. Indeed, in the Smad4 conditional knock-out dendrite and cell body size are not affected and dendrite complexity and number are increased. Together, these results demonstrate an in vivo function for BMPs in the generation of mature sympathetic neuron dendrites. BMPR1 signaling controls dendrite complexity postnatally during the major dendritic growth period of sympathetic neurons.
Reseach Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, Frankfurt/M, Germany, Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Frankfurt/M, Germany, Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, Maryland 20892, Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan 48109-1078, and Department Molecular Biology of the Cell I German Cancer Research Center, D-69120 Heidelberg, Germany.
Afsaneh
A
Majdazari
Jutta
J
Stubbusch
Christian M
CM
Müller
Melanie
M
Hennchen
Marlen
M
Weber
Chu-Xia
CX
Deng
Yuji
Y
Mishina
Günther
G
Schütz
Thomas
T
Deller
Hermann
H
Rohrer
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019843:Archaeal Proteins / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D004622:Embryo, Mammalian; D005456:Fluorescent Dyes / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000172:deficiency / Q000235:genetics; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000378:metabolism
D019843:Archaeal Proteins; D019485:Bone Morphogenetic Proteins; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D014157:Transcription Factors; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; C436950:Dbh protein, Sulfolobus solfataricus; D004259:DNA-Directed DNA Polymerase