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

eLife | 2019

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.

Pubmed ID: 30628891 RIS Download

Associated grants

  • Agency: Israel Science Foundation, International
    Id: 873/14
  • Agency: CIHR, Canada
    Id: 2412/15
  • Agency: International Development Research Centre, International
    Id: 2412/15
  • Agency: Azrieli Foundation, International
    Id: 2412/15
  • Agency: Israel Science Foundation, International
    Id: 2412/15

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