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Fig. 8. Schematic of the proposed interactions between PR and
ß-catenin signaling. In PR-/- glands, cells at
ductal tips are intrinsically responsive to ß-catenin signaling (blue).
In PR+/- glands, PR induces competence to respond to
ß-catenin signaling within a subset of alveolar progenitors along lateral
borders (blue) and possibly designates other bipotent (gray) and ductal
(yellow) progenitor populations. ß-catenin induces alveologenesis at
ductal tips of PR-/- mice and at tips and along lateral
borders of PR+/- mice. It also triggers the secretory
differentiation program, resulting in distended secretion-filled lumen (pink)
in PR-/- mice. Secretory differentiation is restrained by
PR. In the normal virgin mammary gland, PR induces a non-uniform PR
expression pattern and competence to respond to ß-catenin in alveolar
progenitors (blue) during ductal maturation. During early pregnancy, PR-WNT4
signaling induces expansion of ductal progenitors (yellow) to form
side-branches through ß-catenin-independent routes. PR and PRL cooperate
to induce alveologenesis, a process that is ß-catenin-dependent. Later in
pregnancy, PR restrains and PRL promotes alveolar differentiation.
ß-catenin is required for alveologenesis and may participate at multiple
steps in the secretory differentiation pathway.
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