TY - JOUR
T1 - Balance between BDNF and Semaphorins gates the innervation of the mammary gland
AU - Shalom, Hadas Sar
AU - Goldner, Ron
AU - Golan-Vaishenker, Yarden
AU - Yaron, Avraham
N1 - We thank the Yaron lab members for advice and criticism, Lino Tessarollo (NIH) for providing us with the TrkB.T1 KO line, Eran Horenstein’s lab for the use of the microtome, Eli Zelzer’s lab for the help with all the in-situ experiments, Vladimir Kiss for the help with the confocal microscope, Ron Rotkopf for excellent statistical assistance and Oren Schuldiner for critically reading the manuscript. This work was supported by funding to AY from the Israel Science Foundation (873/14) and the Canadian Institutes of Health Research (CIHR), the International Development Research Centre (IDRC), the Israel Science Foundation (ISF) and the Azrieli Foundation (2412/15), The Nella and Leon Benoziyo Center for Neurological Diseases, The Y Leon Benoziyo Institute for Molecular Medicine, Adelis Foundation, Mont-Royal Trust, The Irving B Harris Fund for New Directions in Brain Research, the Joseph D Shane Fund for Neurosciences, and Mr. and Mrs. James Orleans. AY is an incumbent of the Jack and Simon Djanogly Professorial Chair in Biochemistry.
PY - 2019/1/10
Y1 - 2019/1/10
N2 - The innervation of the mammary gland is controlled by brain-derived neurotrophic factor (BDNF), and sexually dimorphic sequestering of BDNF by the truncated form of TrkB (TrkB. T1) directs male-specific axonal pruning in mice. It is unknown whether other cues modulate these processes. We detected specific, non-dimorphic, expression of Semaphorin family members in the mouse mammary gland, which signal through PlexinA4. PlexinA4 deletion in both female and male embryos caused developmental hyperinnervation of the gland, which could be reduced by genetic co-reduction of BDNF. Moreover, in males, PlexinA4 ablation delayed axonal pruning, independently of the initial levels of innervation. In support of this, in vitro reduction of BDNF induced axonal hypersensitivity to PlexinA4 signaling. Overall, our study shows that precise sensory innervation of the mammary gland is regulated by the balance between trophic and repulsive signaling. Upon inhibition of trophic signaling, these repulsive factors may promote axonal pruning.
AB - The innervation of the mammary gland is controlled by brain-derived neurotrophic factor (BDNF), and sexually dimorphic sequestering of BDNF by the truncated form of TrkB (TrkB. T1) directs male-specific axonal pruning in mice. It is unknown whether other cues modulate these processes. We detected specific, non-dimorphic, expression of Semaphorin family members in the mouse mammary gland, which signal through PlexinA4. PlexinA4 deletion in both female and male embryos caused developmental hyperinnervation of the gland, which could be reduced by genetic co-reduction of BDNF. Moreover, in males, PlexinA4 ablation delayed axonal pruning, independently of the initial levels of innervation. In support of this, in vitro reduction of BDNF induced axonal hypersensitivity to PlexinA4 signaling. Overall, our study shows that precise sensory innervation of the mammary gland is regulated by the balance between trophic and repulsive signaling. Upon inhibition of trophic signaling, these repulsive factors may promote axonal pruning.
UR - http://www.scopus.com/inward/record.url?scp=85059798821&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/eLife.41162
DO - https://doi.org/10.7554/eLife.41162
M3 - مقالة
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e41162
ER -