|
Display additional annotations [+]
Gene |
Clone |
Species |
Stages |
Anatomy |
gdf2
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
heart
,
primary heart field
|
gdf2
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
heart
|
acvr1
|
|
laevis
|
NF stage 10.5
|
mesoderm
,
involuted dorsal mesoderm
,
involuted ventral mesoderm
,
endomesoderm
|
acvr1
|
|
laevis
|
NF stage 16
|
pre-chordal neural plate
,
chordal neural plate
,
neural crest
,
mesoderm
,
neural groove
,
[+]
|
acvr1
|
|
laevis
|
NF stage 20
|
neural crest
,
mesoderm
,
lateral plate mesoderm
,
trunk neural crest
,
cranial neural crest
,
[+]
|
acvr1
|
|
laevis
|
NF stage 22
to
NF stage 23
|
mesoderm
,
lateral plate mesoderm
,
anterior dorsal lateral plate region
,
ventral mesoderm
,
dorsal lateral plate mesoderm
|
acvr1
|
|
laevis
|
NF stage 24
to
NF stage 26
|
head region
,
head mesoderm
,
tail region
,
tail bud
,
lateral plate mesoderm
,
[+]
|
acvr1
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
head region
,
dorsal aorta
,
head mesoderm
,
heart
,
lateral plate mesoderm
,
[+]
|
acvr1
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
head region
,
dorsal aorta
,
head mesoderm
,
heart
,
lateral plate mesoderm
,
[+]
|
bmp10
|
|
laevis
|
NF stage 24
to
NF stage 26
|
heart primordium
,
ventral mesoderm
|
bmp10
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
heart
,
primary heart field
|
bmp10
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
heart
,
secondary heart field
|
bmp6
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
late proximal tubule
,
early distal tubule
,
early proximal tubule
,
proximal tubule
,
distal tubule
|
bmp6
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
head mesenchyme
,
proximal tubule
|
bmp5
|
|
laevis
|
NF stage 16
|
pre-chordal neural plate
,
chordal neural plate
|
bmp5
|
|
laevis
|
NF stage 22
to
NF stage 23
|
otic placode
,
heart primordium
,
dorsal lateral plate mesoderm
|
bmp5
|
|
laevis
|
NF stage 24
to
NF stage 26
|
otic vesicle
,
otic placode
,
secondary heart field
|
bmp2
|
|
laevis
|
NF stage 10.5
|
involuting marginal zone
,
involuting marginal zone mesenchymal layer
,
upper blastopore lip
,
endomesoderm
|
bmp2
|
|
laevis
|
NF stage 16
|
mesoderm
,
neural groove
,
anterior
,
ventral mesoderm
|
bmp2
|
|
laevis
|
NF stage 20
|
posterior neural tube
,
anterior neural tube
,
lateral plate mesoderm
,
neural tube
,
ventral mesoderm
|
bmp2
|
|
laevis
|
NF stage 22
to
NF stage 23
|
lateral plate mesoderm
,
ventral mesoderm
|
bmp2
|
|
laevis
|
NF stage 24
to
NF stage 26
|
heart primordium
,
primary heart field
,
ventral mesoderm
,
dorsal lateral plate mesoderm
|
bmp2
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
dorsal aorta
,
heart
,
branchial arch
,
early distal tubule
,
branchial arch 1
,
[+]
|
bmp2
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
head region
,
dorsal aorta
,
head mesoderm
,
heart
,
head mesenchyme
|
bmp4
|
|
laevis
|
NF stage 10.5
|
mesoderm
,
involuting marginal zone
,
involuting marginal zone mesenchymal layer
,
involuted ventral mesoderm
,
endomesoderm
|
bmp4
|
|
laevis
|
NF stage 16
|
neural groove
,
endomesoderm
,
ventral mesoderm
|
bmp4
|
|
laevis
|
NF stage 20
|
neural groove
,
posterior neural tube
,
anterior neural tube
,
endomesoderm
,
neural tube
,
[+]
|
bmp4
|
|
laevis
|
NF stage 22
to
NF stage 23
|
otic placode
,
optic vesicle
,
cardiac mesoderm
,
posterior neural tube
,
anterior neural tube
,
[+]
|
bmp4
|
|
laevis
|
NF stage 24
to
NF stage 26
|
otic vesicle
,
otic placode
,
optic vesicle
,
heart primordium
,
anterior dorsal lateral plate region
,
[+]
|
bmp4
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
spinal cord
,
dorsal aorta
,
heart
,
branchial arch
,
early distal tubule
,
[+]
lateral plate mesoderm
,
trigeminal ganglion
,
branchial arch 1
,
branchial arch 2
,
branchial arch 3
,
branchial arch 4
,
anterior dorsal lateral plate region
,
primary heart field
,
secondary heart field
,
dorsal lateral plate mesoderm
,
distal tubule
|
bmp4
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
spinal cord
,
head region
,
dorsal aorta
,
head mesoderm
,
lateral plate mesoderm
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 10.5
|
neuroectoderm
,
dorsal marginal zone
,
blastopore lip
,
involuted dorsal mesoderm
,
upper blastopore lip
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 16
|
pre-chordal neural plate
,
chordal neural plate
,
neural crest
,
eye primordium
,
neural plate
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 20
|
pre-chordal neural plate
,
chordal neural plate
,
optic vesicle
,
neural plate
,
posterior neural tube
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 22
to
NF stage 23
|
neural crest
,
posterior neural tube
,
anterior neural tube
,
trunk neural crest
,
cranial neural crest
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 24
to
NF stage 26
|
neural crest
,
posterior neural tube
,
anterior neural tube
,
trunk neural crest
,
cranial neural crest
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
spinal cord
,
head region
,
neural crest
,
head mesoderm
,
chordoneural hinge
,
[+]
|
bmpr1b
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
spinal cord
,
head region
,
neural crest
,
head mesoderm
,
cranial neural crest
,
[+]
|
bmpr1a
|
|
laevis
|
NF stage 10.5
|
mesoderm
,
involuted dorsal mesoderm
,
involuted ventral mesoderm
|
bmpr1a
|
|
laevis
|
NF stage 20
|
mesoderm
,
lateral plate mesoderm
,
ventral mesoderm
,
dorsal lateral plate mesoderm
|
bmpr1a
|
|
laevis
|
NF stage 22
to
NF stage 23
|
optic vesicle
,
lateral plate mesoderm
,
anterior dorsal lateral plate region
,
dorsal lateral plate mesoderm
|
bmpr1a
|
|
laevis
|
NF stage 24
to
NF stage 26
|
presomitic mesoderm
,
optic vesicle
,
lateral plate mesoderm
,
anterior dorsal lateral plate region
,
anterior ventral blood island
,
[+]
|
bmpr1a
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
head region
,
dorsal aorta
,
head mesoderm
,
lateral plate mesoderm
,
anterior dorsal lateral plate region
,
[+]
|
bmpr1a
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
head region
,
dorsal aorta
,
head mesoderm
,
lateral plate mesoderm
,
anterior dorsal lateral plate region
,
[+]
|
bmp7.1
|
|
laevis
|
NF stage 10.5
|
involuting marginal zone
,
involuting marginal zone mesenchymal layer
,
involuted ventral mesoderm
,
endomesoderm
|
bmp7.1
|
|
laevis
|
NF stage 16
|
pre-chordal neural plate
,
lateral plate mesoderm
,
anterior placodal area
,
ventral mesoderm
|
bmp7.1
|
|
laevis
|
NF stage 20
|
neural groove
,
lateral plate mesoderm
,
anterior placodal area
,
ventral mesoderm
,
dorsal lateral plate mesoderm
|
bmp7.1
|
|
laevis
|
NF stage 22
to
NF stage 23
|
trigeminal placode
,
optic vesicle
,
lateral plate mesoderm
,
heart primordium
,
anterior dorsal lateral plate region
,
[+]
|
bmp7.1
|
|
laevis
|
NF stage 24
to
NF stage 26
|
trigeminal placode
,
optic vesicle
,
lateral plate mesoderm
,
trigeminal ganglion
,
anterior dorsal lateral plate region
,
[+]
|
bmp7.1
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
dorsal aorta
,
head mesoderm
,
heart
,
eye
,
epibranchial placode
,
[+]
|
bmp7.1
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
head region
,
dorsal aorta
,
head mesoderm
,
lateral plate mesoderm
,
cranial nerve
,
[+]
|
alk
|
|
laevis
|
NF stage 24
to
NF stage 26
|
ventral mesoderm
|
alk
|
|
laevis
|
NF stage 33 and 34
to
NF stage 35 and 36
|
cement gland
,
heart
,
primary heart field
|
alk
|
|
laevis
|
NF stage 37 and 38
to
NF stage 39
|
dorsal aorta
,
heart
,
lateral plate mesoderm
,
blood vessel
,
anterior dorsal lateral plate region
,
[+]
|
|
|
Fig. 1. Expression analysis of BMP ligands and receptors from midgastrulation stage to hemogenic endothelium formation and the description of reagents to inhibit all BMP signaling in blood ontogeny. Primarily, expression in tissues involved in blood stem cell lineage is described. (A) Ligands: bmp2, bmp4, and bmp7 are the principal BMP ligands expressed during gastrulation and onward. At stage 10.5, midgastrulation, bmp2 is expressed in the dorsal mesendoderm. At stage 16, early neurula, bmp2 expression is localized to anterior ventral mesoderm, which encompasses cardiac progenitors and anterior hemangioblasts (AHB). At stage 20–23, bmp2 is expressed along the ventral mesoderm and in lateral plate mesoderm, with signal tapering toward the DLP mesoderm. At stage 26, bmp2 expression is localized along the DLP as well as ventral and cardiac mesoderm. At stages 34–39, bmp2 is expressed in the DA. At stage 10.5, bmp4 is expressed in mesendoderm, with expression diminishing toward dorsal mesendoderm. At stage 16–20, bmp4 is expressed extensively in ventral and lateral mesoderm. From stage 20 onward, bmp4 expression is localized to DLP, encompassing future hemangioblast. At stages 21–26, bmp4 expression is strong along the ventral and lateral plate mesoderm, specifically delineating the DLP tissue at the dorsal most expression domain. At stage 34, bmp4 is expressed in the DA. Bmp5 is not expressed in tissues related to blood lineages, except at stage 38–39, when it is expressed in the DA. Bmp6 is not expressed in HSC lineage. The only expression detectable is transiently in kidney tubules at stage 36. Bmp7 expression at stage 10.5 is localized to ventral most mesendoderm as well as a subset of dorsal mesendoderm. At stages 16–26, bmp7 is expressed along the ventral and lateral plate mesoderm, bordering the kidney field in the dorsal most extent. Bmp7 is strongly expressed in the lateral plate mesoderm for the rest of the developmental stages analyzed. From stage 34 onward, bmp7 is also expressed in the DA. Bmp8 is not expressed during Xenopus development. Bmp9 and bmp10 are expressed in the heart from stage 26 onward. Type I receptors: alk1 is not expressed in early time points; later alk1 expression is primarily restricted to the heart and at stage 38–39 to DA. Alk2 and alk3 are ubiquitously expressed at all stages analyzed. From stage 34 onward, their expression is also observed in the DA. Alk6 is not expressed in blood stem cell lineage but is widely expressed early in dorsal mesoderm and later in neural tissues, neural crest, somites, and notochord. Embryos at stages 10.5 and 34–39 are cleared to enable visualization of the staining of the deeper tissues. For stage 10.5 embryos, D is dorsal and V is for ventral side. For stages 16–20, embryos are visualized from anterior-dorsal (A-D) and anterior-ventral (A-V) angles, except stage 16 bmp4 staining, which is documented from anterior–posterior (A-P) lateral view. From stage 21 onward, the pictures of embryos are taken from lateral view, with anterior–posterior labeled, where it is relevant, on the figure. Expression profile was not determined (nd) for some stages. (Scale bars: 0.5 mm.) (B) BMP2 and BMP4 signal through type I receptors, Alk3 and Alk6. Noggin inhibits signaling by preventing ligands from binding to receptors. DMH1 blocks signaling downstream of Alk3 but not Alk6. (C) BMP5, -6, and -7 signal through type I receptors Alk2, Alk3, and Alk6. Noggin blocks binding of BMP5 and -7 to type I receptors. Noggin does not inhibit signaling downstream of BMP6. DMH1 inhibits Alk2 and Alk3 but not Alk6. (D) BMP9 and -10 signal through type I receptors Alk1 and Alk2. Noggin does not block BMP9 or -10 from binding to receptors. DMH1 blocks Alk1 and Alk2 receptor activity. |