Fig. 5.

Bmp and Wnt signaling regulate region-specific heart morphogenesis. (A–F) Whole-mount in situ hybridization for Bmp4 and Axin2 in controls (A and D) and MesP1-cre; β-catenin^lox/lox (B and E) and MesP1-cre; β-catenin^loxEx3/+ (C and F) mice at the five-somite stage. Note that the expression of Bmp4 and Axin2 is lost in the cardiac crescent of MesP1-cre; β-catenin^lox/lox mice, whereas Bmp4 and Axin2 are overexpressed in MesP1-cre; β-catenin^loxEx3/+ cardiac crescents. (G and H) Quantification of proliferation and apoptosis of controls (solid light-colored bars) and MesP1-cre; β-catenin loss-of-function (striped dark-colored bars) and gain-of-function (dotted medium-colored bars) mutants, as assessed by proportion of phospho-histone H3 (pHH3)- and TUNEL-positive nuclei in FHF (red) and SHF (green). Significant statistical differences between control and mutants are indicated as follows: *, P < 0.05; **, P ≤ 0.01. (I) Average over the total Isl1⁺ cell numbers per section at the four- to six-somite stage and the eight-somite stage. (J) (Left) schemes of mouse embryos show the location and contribution of FHF (red) and SHF (green) cells at crescent (frontal view), heart tube, and looping stages (lateral views). The time points are indicated at which Bmp receptor 1a and Wnt/β-catenin signaling function in heart development. Bmp receptor 1a signaling (red) affects the FHF (red) (a role in SHF development could not be examined), whereas β-catenin signaling (green) affects the SHF (green). (Right) the magnification of the looped heart shows how β-catenin or Bmp receptor 1a signaling might affect heart-specific gene expression. The scheme also indicates where these factors are expressed in the FHF (red) and SHF (green). [Scheme reproduced and modified with permission from ref. 1 (Copyright 2006, Cell) and ref. 2 (Copyright 2005, Nat Rev Genet).]