Balance between BDNF and Semaphorins gates the innervation of the mammary gland

Hadas Sar Shalom; Ron Goldner; Yarden Golan-Vaishenker; Avraham Yaron

doi:10.7554/eLife.41162

Balance between BDNF and Semaphorins gates the innervation of the mammary gland

Hadas Sar Shalom
, Ron Goldner
, Yarden Golan-Vaishenker
, Avraham Yaron^*

^*Corresponding author for this work

Department of Biomolecular Sciences

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e41162
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.41162
Publication status	Published - 2019

Funding

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.

All Science Journal Classification (ASJC) codes

General Neuroscience
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.41162Licence: CC BY

Cite this

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title = "Balance between BDNF and Semaphorins gates the innervation of the mammary gland",

abstract = "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.",

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AU - Goldner, Ron

AU - Golan-Vaishenker, Yarden

AU - Yaron, Avraham

PY - 2019

Y1 - 2019

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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.

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Balance between BDNF and Semaphorins gates the innervation of the mammary gland

Abstract

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