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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.