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Int J Dev Biol
2017 Jan 01;616-7:465-470. doi: 10.1387/ijdb.170037af.
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Expression of the ALK1 family of type I BMP/ADMP receptors during gastrula stages in Xenopus embryos.
Leibovich A
,
Steinbeißer H
,
Fainsod A
.
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Multiple members of the transforming growth factor beta (TGFβ) family of secreted factors play central inductive and patterning roles during embryogenesis. During gastrulation in vertebrates, the bone morphogenetic protein (BMP) sub-family is linked to formation of the embryonic organizer, Spemann's organizer in Xenopus, and dorsal-ventral mesoderm patterning. Our knowledge regarding the BMP receptors mediating this signaling is still very incomplete. The BMPR1A (ALK3) and BMPR1B (ALK6) receptors are known to mediate the BMP4 signal. These receptors belong to the ALK1 subfamily of type I receptors that also includes ACVR1 (ALK2), and ACVRL1 (ALK1). We studied by qPCR and in situ hybridization the spatio-temporal expression patterns of ALK2 and ALK1 and compared them to ALK3 and ALK6, and to the main BMPs expressed during gastrulation, i.e., BMP4, BMP7, BMP2, and ADMP, in an attempt to establish a link between ligands and receptors. There is extensive overlap between BMP4, and ALk3 and Alk6 expression, supporting their functional interaction. Robust Alk6 expression was observed from mid-gastrula. Animal region expression of both receptors shows co-expression with BMP4 and BMP7. Alk2 transcripts were detected within the organizer, overlapping with its proposed ligand, ADMP, suggesting a probable function within the organizer. Alk1 is very weakly expressed during gastrula, but its transcripts were localized to the lateral marginal zone flanking the organizer domain. No receptor closely matched the maternal BMP2 expression, although Alk2, Alk3, and Alk6, have transcripts of maternal origin. Our analysis shows that the BMP ligands and their receptors exhibit dynamic expression patterns during gastrula stages.
Fig. 1. The ALK1 family of type I bone morphogenetic protein (BMP) receptors. Phylogenetic tree of the ALK1family of type I BMP receptors. Protein sequences from Xenopus laevis and Xenopus tropicalis, human and mouse, were included in the analysis. The analysis subdivided the ALK1 sub-families, ALK6, ALK3, ALK2, and ALK1. For each sub-family, the percent sequence identity to the relevant Xenopus laevis protein is shown.
Fig. 2. Temporal expression of the Alk1 receptor family and the main bone morphogenetic protein (BMP ) ligands during gastrulation. RNA samples from X. laevis embryos from early cleavage (st. 4-5) to late neurula (st. 22) stages were analyzed by qPCR. Temporal pattern of the receptor gene expression; (A) Alk2 and Alk3, (C) Alk1 and Alk6. Expression of the ligand genes as a function of developmental stage; (B) BMP4, BMP7 and ADMP and (D) BMP2. (E) Relative transcript abundance of the receptor and ligand genes during early/mid-gastrula (st. 10.5). (F) Comparison of the expression levels between ADMP/BMP4 and Alk2/Alk3 from late blastula (st. 9) to early neurula (st. 15) stages. The gray shading marks gastrula stages.
Fig. 3. Spatial localization of the Alk1 family transcripts in gastrula embryos. X. laevis embryos at early/mid-gastrula (st. 10.5) were dissected into four regions, the animal cap (AC), and the dorsal, lateral, and ventral, regions of the marginal zone (DMZ, LMZ, and LMZ, respectively). RNA from each embryonic region was analyzed by qPCR. Relative transcript abundance in each region was normalized for most genes to the AC level of expression, only for BMP7 the level of expression in the VMZ was used for normalization. (A) Relative transcript abundance of the ALK1 family receptors. (B) Relative spatial localization of the BMP ligand transcripts. (C) The transcript localization of the chordin, MyoD, and sizzled genes was analyzed to determine the dissection accuracy for the DMZ, LMZ+VMZ, and VMZ respectively. A schematic representation of the embryo is shown.
Fig. 4 (left). The Alk2 gene encodes an organizer-expressed gene. Whole-mount ISH analysis of the Alk2, Alk3, and Alk6 genes from early cleavage to late gastrula stages. (A-C) Four-cell embryos, animal view. (D-F) Late blastula stage (st. 9), animal view. (G-I) Early gastrula embryos (st. 10.25), vegetal view. The dorsal lip of the blastopore is marked with a dashed line. (J-L) Late gastrula (st. 11.5) expression, vegetal view.
Fig.5 (right) expression marks the epiboly of the prospective ectoderm. Whole-mount ISH analysis of BMP7 expression from late blastula to early neurula. Lateral views of st. 9 (A), st. 10 (B), st. 10.5 (C), and st. 11 (D) embryos, and posterior animal view of st. 13 (E) embryo.
Fig. 6. Expression of the ALK1 receptor family and the bone morphogenetic protein (BMP) ligands during gastrula. Schematic summary of the expression of the type I receptors Alk1, Alk2, Alk3, and Alk6, and the BMPs, BMP2, BMP4, BMP7, and ADMP. The summary focuses on the marginal zone expression of the different genes and relates to the dissection scheme.
