BMP and BMP receptor expression during murine organogenesis - PubMed (original) (raw)

BMP and BMP receptor expression during murine organogenesis

Shahab M Danesh et al. Gene Expr Patterns. 2009 Jun.

Abstract

Cell-cell communication is critical for regulating embryonic organ growth and differentiation. The Bone Morphogenetic Protein (BMP) family of transforming growth factor beta (TGFbeta) 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.

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Figures

Fig. 1. Expression of Bmp ligands and the BMP antagonist noggin during embryogenesis

Whole mount in situ hybridization of embryos E7.5–E10.5 for the following transcripts: Panels A) Bmp2; Panels B) Bmp4; Panels C) Bmp7; and Panels D) noggin. Panels 1) E7.0–7.5 embryos are frontal views with head facing forward, allantois in back, pointing up, and yolk sac still attached, except panel B1 which is slightly tilted to the left. Panel A1 and B1 are E7.25, C1 is E7.5 and panel D1 is E7.0. Panels 2) E8.25–E8.5 unturned embryos are shown in frontal views, with head and open AIP facing forward; yolk sac is still attached. Panels 3) E8.75 are shown in process of turning, or shortly after turning. Panels 4–6) E9.0–E10.5 embryos have completed turning and are shown in lateral view facing left. Red dashed lines outline dorsal aorta. All embryos are shown anterior up, dorsal on right. Arrow in panels A3 and A4 indicates atrioventricular canal (avc); in panel A4, red arrowhead shows mesonephros and black arrowhead points to aorta; small black arrowheads in panels D3–D6 indicate isthmus. Embryonic structures and tissues are annotated in top panel schematics, which represent embryos shown in photographs below. Annotations as follows: a, allantois; aip, anterior intestinal portal; ao, aorta; avc, atrioventricular canal; b, branchial arches; cc, pre-cardiac crescent; d, diencephalon; g, pre-gut endoderm; h, heart; hd, head; l, liver diverticulum; lb, limb bud; lpm, lateral plate mesoderm; m, mesonephros; n, nasal placode; no, notochord; nf, neural folds; ov, otic vesicle; s, somites; sv, sinus venosus; t, tail; y, yolk sac; ysc, yolk sac constriction.

Fig. 2. Expression of Bmp ligands and the BMP antagonist noggin in developing tissues

Whole mount in situ hybridization of embryos for the following transcripts: Panels A) Bmp2; Panels B) Bmp4; Panels C) Bmp7; and Panels D) noggin. Panels 1) Close up view of embryonic head, showing open neural tube and fusing headfolds at E8.75. Anterior is up, dorsal view. Arrows in A1 point to neural folds. Panels 2) Close up view of anterior portion of E9.0 embryo, highlighting head, heart, sinus venosus, branchial arches, otic vesicle, liver diverticulum and anterior somite expression. Anterior is up, dorsal is on right. Arrows indicate neuron populations. Panels 3) Close up on dorsal midsection of embryo, showing neural tube, anterior somites and developing limb buds at E9.0. View of dorsal surface of neural tube, head is up, tail points away from viewer. Panels 4) Close up view of E10.5 developing gut tube dissected away from the embryo, highlighting expression in esophagus/trachea, lungs, stomach and anterior edge of pancreas. Dotted line indicates dorsal midline of the gut tube. At this stage, the gut tube is beginning to break symmetry and turn left. Anterior is up, dorsal view. Panels 5) Close up views of dissected E10.5 hearts. Ventroanterior view, with outflow tract in front and AVC behind, except inset in A5 where view is dorsoposterior showing Bmp2 expression in AVC. Note that strong expression in AVC can be seen through transparent outflow tract in main panel A5. Panels 6) Close up view of E10.5 somites (numbers 12–25). Ventral is up, anterior to right, lateral view. Small black arrowhead in panel D1 indicates isthmus. Annotations as follows: a, aorta; avc, atrioventricular canal; b, branchial arches; e, esophagus; fl, forelimb; g, gut; hd, head; h, heart; hl, hindlimb; l, liver diverticulum; la, left atrium; lb, limb bud; lu, lung; lv, left ventricle; ms, midline seam of neural tube; nf, neural folds; nt, neural tube; oc, optic cup; ot, outflow tract; ov, otic vesicle; p, pancreas; pi, pituitary; ra, right atrium; rv, right ventricle; s, somite; st, stomach; th, thyroid primordium.

Fig. 3. Sections showing Bmp ligand and noggin expression

Sections of whole mount in situ hybridization of embryonic tissues for the following transcripts: Panels A) Bmp2; Panels B) Bmp4; Panels C) Bmp7; and Panels D) noggin. Panels 1) Transverse sections of neural tubes and headfolds at E8.75. Dorsal is up. Panels 2) Transverse sections of heart at E9.0 showing both atria and ventricle. Panels 3) Transverse sections through developing limb buds at E9.0, showing outer epidermis (top) and underlying limb mesenchyme. Panels 4) Transverse sections of stomach at E10.5, showing both gut epithelium and gut mesoderm. Stomach epithelium outlined with dashed lines; dorsal is to the right. Red dotted line in panel B4 shows embryonic midline. Panels 5) Transverse sections through developing lung buds. Lung bud epithelium outlined with dashed lines. Anterior is up, dorsal view. Annotations as follows: a, atria; aer, apical ectodermal ridge; avc, atrioventricular canal; e, epithelium; he, head epidermis; le, limb epidermis; lm, limb mesenchyme; m, mesenchyme; me, mesogastrium; nf, neural folds; v, ventricle.

Fig. 4. Expression of Bmp receptors during embryogenesis

Whole mount in situ hybridization of embryos E7.5–E10.5 for the following transcripts: Panels A) Bmpr1a; Panels B) Bmpr1b; and Panels C) BmprII. Panels 1) E7.25–7.0 embryos are frontal views with head facing forward, allantois in back, pointing up, and yolk sac still attached. A1 and C1 are E7.25; B1 is E7.5. Panels 2) E8.25–E8.5 unturned embryos are shown in frontal views, with head and open AIP facing forward: and yolk sac is still attached, except for panel B2 where yolk sac has been removed. In panel B2, inset shows dorsal view and expression in hindbrain rhombomere 3. Panels 3) E8.75 are shown in process of turning, or shortly after turning. Panels 4–6) E9.0–E10.5 embryos have completed turning and are shown in lateral view facing left. All embryos are shown anterior up, dorsal on right. Embryonic structures and tissues are annotated in top panel schematics, which represent embryos shown in photographs below. Arrowheads in A3 and A4 show low levels of expression in heart. Annotations as follows: a, allantois; aip, anterior intestinal portal; ao, aorta; avc, atrioventricular canal; cc, pre-cardiac crescent; d, diencephalon; g, pre-gut endoderm; h, heart; hd, head; l, liver diverticulum; lb, limb bud; lpm, lateral plate mesoderm; m, mesonephros; n, nasal placode; nf, neural folds; ov, otic vesicle; s, somites; sv, sinus venosus; t, tail; y, yolk sac; ysc, yolk sac constriction.

Fig. 5. Expression of Bmp receptors in developing tissues

Whole mount in situ hybridization of embryos for the following transcripts: Panels A) Bmpr1a; Panels B) Bmpr1b; and Panels C) BmprII. Panels 1) Close up view of embryonic head, showing open neural tube and fusing headfolds at E8.75. Anterior is up, dorsal view. In panel B1, r3 indicates rhombomere 3. Panels 2) Close up view of anterior portion of E9.0 embryo, highlighting head, heart, sinus venosus, branchial arches, otic vesicle, liver and anterior somite expression. Anterior is up, dorsal is on right. Panels 3) Close up on dorsal midsection of embryo, showing neural tube, anterior somites and developing limb buds at E9.0. View of dorsal surface of neural tube, head is up, tail points away from viewer. Panels 4) Close up view of E10.5 developing gut tube dissected away from the embryo, highlighting expression in esophagus/trachea, lungs, stomach and anterior edge of pancreas. At this stage, the gut tube is beginning to break symmetry and turn left. Anterior is up, dorsal view. Panels 5) Close up views of dissected E10.5 hearts. Ventroanterior view, with outflow tract in front and AVC behind. Panels 6) Close up view of E10.5 somites (numbers 12–25). Ventral is up, anterior to right, lateral view. Annotations as follows: a, aorta; avc, atrioventricular canal; b, branchial arches; e, esophagus; fl, forelimb; g, gut; hd, head; h, heart; hl, hindlimb; l, liver diverticulum; la, left atrium; lb, limb bud; lu, lung; lv, left ventricle; nf, neural folds; nt, neural tube; oc, optic cup; ot, outflow tract; ov, otic vesicle; p, pancreas; ra, right atrium; rv, right ventricle; s, somite; st, stomach.

Fig. 6. Sections showing Bmp receptor expression

Sections of whole mount in situ hybridization of embryonic tissues for the following transcripts: Panels A) Bmpr1a; Panels B) Bmpr1b; and Panels C) BmprII. Panels 1) Transverse sections of neural tubes and headfolds at E8.75. Dosal is up. Panels 2) Transverse sections of heart at E9.0 showing both atria and ventricle. Panels 3) Transverse sections through developing limb buds at E9.0, showing outer epidermis and underlying limb mesenchyme. Panels 4) Transverse sections of stomach at E10.5, showing both gut epithelium and gut mesoderm. Stomach epithelium outlined with dashed lines; dorsal is to the right. Panels 5) Transverse sections through developing lung buds. Lung bud epithelium outlined with dashed lines. Anterior is up, dorsal view. Annotations as follows: a, atria; aer, apical ectodermal ridge; avc, atrioventricular canal; e, epithelium; he, head epidermis; le, limb epidermis; lm, limb mesenchyme; m, mesenchyme; me, mesogastrium; nf, neural folds; v, ventricle.

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BMP and BMP receptor expression during murine organogenesis - PubMed (original) (raw)