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Table 1 Regulators of mammary morphogenesis and their agonists, antagonists, downstream targets and realm of influence

From: Key stages in mammary gland development: The cues that regulate ductal branching morphogenesis

Regulator Agonists Antagonists Targets Effects
GH-R (st) GH (pit)   IGF-1 (st) General
IGF-1R (ep) IGF-1 (st) IGFBPs (st) Unknown General
ER-α (st/ep) E1/E2 (ov)   Amphiregulin et al. General
PR-B (st?) ER, P (ov)   Wnt4, RANKL Tertiary branching
EGFR (st) Amphiregulin (ep) Sprouty? MMPs, FGFs et al. General
Amphiregulin (ep) ER, ADAM17 (ep) HSPGs EGFR (st) General
ADAM17 (ep) PPCs et al. TIMP3 (ep) Amphiregulin (ep) General
MMP-14 (st) EGFR, PPCs et al. TIMPs 2–4 MMP-2, Coll I General
MMP-2 (st?) TGF-β, ER, MMP-14 TIMPs 1–4 Coll I et al.? Elongation
MMP-3 (st) Epimorphin et al. TGF-β, TIMPs Unknown Secondary branching
FGFR2 (ep) FGFs (st) Sprouty2 (ep) Unknown TEBs
ErbB2 (ep) Unknown Unknown Unknown TEBs
Epimorphin (st/me) Metalloenzymes Unknown C/EPBβ, MMPs Branching
TGF-β1 (ep) ER, MMPs, plasmin LAP TGF-βRI/II, MMPs Spacing
CSF-1R (mφ) CSF-1 (ep)   Mφ recruitment TEBs
CCR3 (eos) Eotaxin   Eos recruitment Branching
Integrin α2β1 (ep) Laminins, collagens    TEBs, ducts
DDR1 (ep) Collagens    TEBs, ducts
  1. ADAM, a disintegrin and metalloproteinase; CCR, CC chemokine receptor; Coll, collagen; CSF, colony-stimulating factor; DDR, discoidin domain receptor; EGFR, epidermal growth factor receptor; eos, eosinophil; ep, epithelial; E1/E2, estrone/estradiol; ER, estrogen receptor; FGF, fibroblast growth factor; FGFR, FGF receptor; GH, growth hormone; GH-R, growth hormone receptor; HSPG, heparan sulfate proteoglycan; IGF-1, insulin-like growth factor-1; IGF-1R, IGF-1 receptor; IGFBPs, IGF-binding proteins; LAP, latency-associated peptide; me, myoepithelial; MMP, matrix metalloproteinase; mφ, macrophage; ov, ovarian; pit, pituitary; PPC, proprotein convertase; P, progesterone; PR, progesterone receptor; RANKL, receptor activator of nuclear factor κB (RANK) ligand; st, stromal; TEB, terminal end bud; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinases. Required sources are provided in parentheses.