BMP and BMP receptor expression during murine organogenesis

Abstract

Cell-cell communication is critical for regulating embryonic organ growth and differentiation. The Bone Morphogenetic Protein (BMP) family of transforming growth factor β (TGFβ) molecules represents one class of such cell-cell signaling molecules that regulate the morphogenesis of several organs. Due to high redundancy between the myriad BMP ligands and receptors in certain tissues, it has been challenging to address the role of BMP signaling using targeting of single Bmp genes in mouse models. Here, we present a detailed study of the developmental expression profiles of three BMP ligands (Bmp2, Bmp4, Bmp7) and three BMP receptors (Bmpr1a, Bmpr1b, and BmprII), as well as their molecular antagonist (noggin), in the early embryo during the initial steps of murine organogenesis. In particular, we focus on the expression of Bmp family members in the first organs and tissues that take shape during embryogenesis, such as the heart, vascular system, lungs, liver, stomach, nervous system, somites and limbs. Using in situ hybridization, we identify domains where ligand(s) and receptor(s) are either singly or co-expressed in specific tissues. In addition, we identify a previously unnoticed asymmetric expression of Bmp4 in the gut mesogastrium, which initiates just prior to gut turning and the establishment of organ asymmetry in the gastrointestinal tract. Our studies will aid in the future design and/or interpretation of targeted deletion of individual Bmp or Bmpr genes, since this study identifies organs and tissues where redundant BMP signaling pathways are likely to occur.

RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis

“…The deeper muscles are incompletely stained, due to limited penetration of the tissue by probe and antibody. Expression domains of the Neogenin receptor according to (Fitzgerald et al, 2006;Gad et al, 1997;Mawdsley et al, 2004, this study); BMP2,4,6 (Andr ee et al Chapman et al, 2002;Danesh et al, 2009;Zhou et al, 2010), Shh (Roelink et al, 1995;Marti et al, 1995), mouse RGMa and RGMb (Schmidtmer and Engelkamp, 2004;Niederkofler et al, 2004;Oldekamp et al, 2004); Xenopus RGMa and RGMb Wilson and Key, 2006;Gessert et al, 2008;Kee et al, 2008), and zebrafish RGMa and RGMb (Samad et al, 2004;Bian et al, 2011). Hyphens indicate absence of corresponding expression domains for the chicken paralogs.…”

The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo

“…These findings suggest that when BMP4 and BMP7 precursor proteins are coexpressed in the same cell type in vivo, they preferentially form heterodimers rather than either homodimer. Because expression of Bmp4 and Bmp7 overlap extensively throughout development (32), it is likely that they signal as heterodimers in at least some contexts. However, the degree of heterodimer formation will be dependent on the relative level of expression of BMP class I and class II precursor proteins in a given cell type.…”

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

“…5 However, considerably less is known about BMP4 expression and function in normal adult tissues. Genes and signaling pathways that normally participate in developmental processes have been shown to also be reactivated in cancer pathogenesis.…”

“…4 The mouse embryos die between 6.5 and 9.5 days postcoitum and suffer from defects in gastrulation and mesoderm formation. [3][4][5] Bmp4 expression is also detected later during organogenesis of the kidney, tooth, lung and gut as well as during skeletogenesis, limb patterning and mammary gland development. 3,6,7 On a cellular level, BMPs are able to modulate cell proliferation, differentiation, survival, migration and even cell fate.…”