Abstract
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.
Copyright: © 2024 by the authors.
Grants and funding
We acknowledge core support from the UCSC Institute for the Biology of Stem Cells and California Institute for Regenerative Medicine (CIRM) Shared Stem Cell Labs (RRID:SCR_021353) and Microscopy (RRID:SCR_021135) Facilities (CL1-00506-1,2), CIRM Major Facilities (FA1-00617-1) and National Institutes of Health confocal grant: 1S10OD23528-01. This work was supported by the National Institutes of Health: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIHCD) under award number R01HD098722 to L.H. and T32HD108079 Training Award to J.M. Other support for individuals was from a California Institute of Regenerative Medicine (CIRM) training grant (EDUC-12759) to R.M; National Institutes of Health IMSD 2R25GM058903-16A1, ARCS foundation and National Science Foundation (DGE 1339067) GRFP support to O.C.