Disruption of reelin signaling alters mammary gland morphogenesis

Elvira Khialeeva, Timothy F Lane, Ellen M. Carpenter

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Reelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalDevelopment
Volume138
Issue number4
DOIs
StatePublished - Feb 15 2011

Keywords

  • Dab1
  • Ductal branching
  • Ductal elongation
  • Extracellular matrix
  • Mammary epithelial cell
  • Mouse
  • Reeler

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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