Expression of transforming growth factors BMP-4 and TGFβ1 in the human embryonic AGM region.

Immunohistochemical analysis on transverse sections of human embryos and yolk sac. (A) Within the AGM region at 34 days, a gradient of BMP-4 protein exists across the dorsoventral axis at the level of the AGM region. BMP-4 is expressed in the ventral mesoderm (below thin arrows), which includes the dorsal aorta (da), cardinal veins (cv), and mesonephros (m), whereas the dorsal mesoderm (above thin arrows), between the dorsal aorta and neural tube (nt), is predominantly negative. (B) Higher magnification of (A) in the region of the dorsal aorta. BMP-4 expression is polarized to the ventral stromal region (s) underlying the intra-aortic hematopoietic cluster (hc). (C) In contrast, in a younger 28-day-old embryo, BMP-4 is expressed at low level in both ventral and dorsal mesoderm, with few highly positive cells. (D) However, as shown by a higher magnification of (C), BMP-4 expression is at this stage restricted to the thin “stromal” layer (s) underlying the ventral wall of the aorta from which a cluster of cells (hc) can be seen emerging. (E) At more caudal levels (34 days), no intra-aortic clusters are visible and BMP-4 expression is markedly lower than in the AGM, consistent with an anterior-posterior progression of development during embryogenesis. (F) At 38 days gestation, BMP-4 expression within the AGM region is relatively uniform around the entire aorta and is not polarized to the ventral wall. (G) Cells expressing BMP-4 (arrows) are specifically associated with blood islands (bi) in the embryonic yolk sac (31 days). (H) TGFβ1 is expressed by cells within the intra-aortic cluster (hc). Uniformly low level expression is detected around the aorta. (Original magnification: A, C, ×15; B, D, E, G, H ×78, F ×36).