Temporal analysis of the early BMP functions identifies distinct anti-organizer and mesoderm patterning phases

Abstract

BMP signaling performs multiple important roles during early embryogenesis. Signaling through the BMP pathway is mediated by different BMP ligands expressed in partially overlapping temporal and spatial patterns. Assignment of different BMP-dependent activities to the individual ligands has relied on the patterns of expression of the various BMP genes. Temporal analysis of BMP signaling prior to and during gastrulation was performed using glucocorticoid-controlled Smad proteins. Overexpression of the BMP-specific Smad1 and Smad5 revealed that suppression of Spemann's organizer formation in Xenopus embryos can only take place by activating the BMP pathway prior to the onset of gastrulation. Blocking BMP signaling with the inhibitory Smad, Smad6, results in dorsalized embryos or secondary axis induction, only when activated up to early gastrula stages. BMP2 efficiently represses organizer-specific transcription from the midblastula transition onwards while BMP4 is unable to prevent the early activation of organizer-specific genes. Manipulation of the BMP pathway during mid/late gastrula affects mesodermal patterning with no external phenotypic effects. These observations suggest that the malformations resulting from inhibition or promotion of organizer formation, ventralized or dorsalized, respectively, are the result of a very early BMP function, through its antagonism of organizer formation. This function is apparently fulfilled by BMP2 and only at its latest phase by BMP4. Subsequently, BMP functions in the patterning of the mesoderm with no apparent phenotypic effects.

Temporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes

“…While it had been established in Xenopus and zebrafish that BMP signaling patterns most of the DV axis from mid-blastula through gastrula stages, there was only a general understanding of the broad tissue types that were being patterned (Fig. 1a) [148,191,192]. Additionally, the tail is not completely specified within that time window.…”

Patterning the earlyXenopusembryo

“…What then are the states of determination of equatorial cells when BMP function is blocked? A key analysis here has been to manipulate BMP signaling in a temperature-sensitive manner (Marom et al, 2005). BMP suppression at the blastula stage causes upregulation of organizer genes (goosecoid), causing secondary axis (neural and somite tissue) formation.…”

Dynamic determinations: patterning the cell behaviours that close the amphibian blastopore

“…Cell fate along this axis is regulated by 'ventralizing' signals from the ventral sector, countered by dorsal antagonists (De Robertis & Kuroda 2004;Lane et al 2004;Marom et al 2005;Heasman 2006). The progress of MIB, given its association with dorsal notochordal and somitic tissue, is a read-out of this process.…”