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SLIT Loss or Sequestration Increases Mammary Alveologenesis and Lactogenesis
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https://doi.org/10.17912/micropub.biology.001264Abstract
SLITs comprise a family of secreted proteins that function as ligands for Roundabout (ROBO) receptors. Previous research showed that ROBO1 promotes the differentiation of milk-producing alveolar cells by inhibiting Notch signaling in mammary luminal cells. Here, we show enhanced alveolar development and increased milk production in Slit2-/-;Slit3-/- knockout mammary gland epithelia. This result can also be achieved by intraperitoneal delivery of recombinant ROBO1 extracellular domain fragment, ROBO1-5Ig-Fc, which sequesters SLITs. Together, our phenotypic studies suggest that SLITs restrict alveologenesis and lactogenesis by inhibiting ROBO1.
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