Expression of the ALK1 family of type I BMP/ADMP receptors during gastrula stages in Xenopus embryos

Abstract

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.

ADMP controls the size of Spemann's organizer through a network of self-regulating expansion-restriction signals

“…ADMP has been shown to bind the type I receptor, ACVR1 (ALK2) [ 17 ], while the common BMP receptors, BMPR-Ia (ALK3) and BMPR-Ib (ALK6) and the type II receptor, BMPR-II, do not bind ADMP or inhibit its activity [ 17 , 21 ]. We have recently shown that Alk2 is expressed within the organizer and it is co-expressed with ADMP [ 19 ]. As the putative, dorsal ADMP receptor, ALK2 should be involved in the organizer-promoting function of ADMP (Figs.…”

“…Therefore, we focused on ALK1 (ACVRL1) as a putative second ADMP receptor. Recently we described the Alk1 expression pattern during early gastrula [ 19 ]. Alk1 is a weakly expressed gene during gastrula stages, and its transcripts are most abundant in the lateral marginal zone (LMZ), just flanking the organizer domain.…”

“…Several ADMP reported characteristics are inconsistent with a simple BMP-like role. Foremost, ADMP is robustly expressed in the dorsal region, the future organizer [ 16 , 19 ], and it is a robust repressor of the organizer itself [ 18 , 20 ]. ADMP is involved in the transition of the organizer, from head- to trunk-promoting, in a concentration-dependent manner [ 21 , 22 ].…”

“…We show that during early gastrula (stage 10–10.25) organizer-specific gene expression is dependent on normal ADMP activity levels. We show that this activity is mediated by the dorsally localized activin A type I receptor, ACVR1 (also known as activin receptor-like kinase-2, ALK2) [ 19 ]. These observations support a novel early function for ADMP as a “typical” organizer gene, in agreement with its localized expression within this embryonic region.…”

“…This anti-organizer activity is mediated by a different putative ADMP type I receptor, ACVRL1 (ALK1). ALK1 is expressed laterally [ 19 ] and mediates the organizer-repressive activity of ADMP. The ADMP signaling network was modeled to show that it can control the size of the organizer and that it relies on the availability, expression timing, and spatial localization of its receptors.…”