FIG. 1.

Genetic deficiency of brain-derived neurotrophic factor (BDNF), neurotropin-3 (NT-3), or tropomyosin-related kinase receptor C (trKC) causes cardiac and vascular defects in the developing mammalian heart. I: BDNF^−/− neonate mice exhibit ventricular wall hemorrhage. Histological analyses of BDNF^+/+ (A, C, and E) or BDNF^−/− (B, D, and F–H) littermates killed at P0. Hematoxylin and eosin-stained sections reveal hemorrhage in the epicardial third of both right and left ventricular walls of BDNF^−/− neonates (B and D, arrowheads) and an atrial septal defect (B). Pulmonary hemorrhage is detectable in BDNF^−/− (F) but not BDNF^+/+ littermates (E). Hemorrhage was not detectable in other organs, such as kidneys (G) as well as skin and spinal cord (H). Ra and la, right and left atria; rv and lv, right and left ventricles; asd, atrial septal defect; s, skin; m, skeletal muscle; vb, vertebral body; sc, thoracic spinal cord. Scale bars, 150 μm (A and B), 50 μm (C and D), 100 μm (E–H). [From Donovan et al. (70), with permission from Development.] II: schematic representation of cardiac abnormalities in NT-3^−/− neonate mice. Schematic representations of normal cardiac anatomy(A), the NT-3^−/− mutant heart (B), the aorta (AO), ductus arteriousus (DA), right and left atrium (RA, LA), right and left ventricle (RV, LV), tricuspis (TV), and mitral (MV) valve are indicated. [From Donovan et al. (69), reprinted by permission from Macmillan Publishers Ltd.] III: table showing heart abnormalities in trkC^−/− mice. [Adapted from Tessarollo et al. (258).]