Hedgehog and Gli signaling in embryonic mammary gland development - PubMed (original) (raw)

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Hedgehog and Gli signaling in embryonic mammary gland development

May Yin Lee et al. J Mammary Gland Biol Neoplasia. 2013 Jun.

Abstract

The first mouse mutation associated with a heritable defect in embryonic mammary gland development was Extratoes. It represents a functional null-mutation of the gene encoding Gli3, which is best known as a transcription factor mediating canonical Hedgehog (Hh) signaling. Here we review the roles of Hh and Gli proteins in murine embryonic mammary development. We propose that an off-state for Hh signaling, mediated by Gli3-repressor, is determinant for induction of a mammary instead of hair follicle fate in the trunk surface ectoderm.

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Figures

Fig. 1

Fig. 1

Expression patterns of Gli1, Gli2 and Gli3, and models of tissue- and molecular interactions involving Gli3 in mammary development. a–q Cross-sections of wild-type embryos and (r–w) Gli3 Xt-J/Xt-J embryos at E11.5-E13.5 hybridized with 35S-labeled RNA-probes for Gli1, Gli2 and Gli3. Magnification of r-w is twice that of a–q. Insets in t’ and u’ present wild-type MR2 from l’ respectively m’ at the same magnification. MRs are indicated by number. Black arrow in a–c indicates emerging MR3 at E11.5. White arrowheads in r’, t’ s’ and u’ point to MM expression. x Cartoon of a lateral view of a mouse embryo. Between E10.5 and E11.5 Gli3 is expressed in the limb buds and all somites (outlined in gray and numbered). Gray shades represent overlapping in expression with Fgf10, the intensity positively correlating with level of Fgf10 expression. Note the proximity of the overlapping somitic expression to MR3 and MR2, and overlapping limb mesenchymal expression to MR1, MR2, MR4 and MR5. MR1 and MR5 are hidden behind the limbs. y Model exclusively for formation of MR3: See main text for explanation. z Model for Gli3-mediated repression of Gli1 in the ME (bud shape) and contiguous MM (darker shade of gray surrounding mammary bud), based on expression data in panels a–w and in [5, 6]. In the absence of Gli3, Gli1 is misexpressed in the MM of MR1, MR2 and MR4, indicating Gli3R normally represses Gli1 expression. Whether this occurs tissue-autonomously (intact block arrow) or via tissue interactions (broken block-arrow) remains unclear. Abbreviations: li: liver, r: rib primordium, st: stomach, wt: wild-type

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