What are the roles of retinoids, other morphogens, and Hox genes in setting up the vertebrate body axis?

Abstract

Summary This article is concerned with the roles of retinoids and other known anterior–posterior morphogens in setting up the embryonic vertebrate anterior–posterior axis. The discussion is restricted to the very earliest events in setting up the anterior–posterior axis (from blastula to tailbud stages in Xenopus embryos). In these earliest developmental stages, morphogen concentration gradients are not relevant for setting up this axis. It emerges that at these stages, the core patterning mechanism is timing: BMP‐anti BMP mediated time space translation that regulates Hox temporal and spatial collinearities and Hox‐Hox auto‐ and cross‐ regulation. The known anterior–posterior morphogens and signaling pathways––retinoids, FGF's, Cdx, Wnts, Gdf11 and others––interact with this core mechanism at and after space–time defined “decision points,” leading to the separation of distinct axial domains. There are also other roles for signaling pathways. Besides the Hox regulated hindbrain/trunk part of the axis, there is a rostral part (including the anterior part of the head and the extreme anterior domain [EAD]) that appears to be regulated by additional mechanisms. Key aspects of anterior–posterior axial patterning, including: the nature of different phases in early patterning and in the whole process; the specificities of Hox action and of intercellular signaling; and the mechanisms of Hox temporal and spatial collinearities, are discussed in relation to the facts and hypotheses proposed above.

A Tribute to Lewis Wolpert and His Ideas on the 50th Anniversary of the Publication of His Paper ‘Positional Information and the Spatial Pattern of Differentiation’. Evidence for a Timing Mechanism for Setting Up the Vertebrate Anterior-Posterior (A-P) Axis

“…There are various morphogens that are thought to be involved in setting up the main body's A-P axis and the limb's P-D axis. Their roles in relation to the timing mechanism considered here have been discussed above and elsewhere [41,43]. However, this aspect deserves further attention.…”

“…Please note that each of these external pathways acts only over a certain limited developmental period and only over a certain limited part of the A-P axis. The (extensive) evidence for this mechanism is given in three recent reviews [19,41,43]. Space prohibits repeating it here again.…”

“…The yellow background shows that TC happens in the availability of a high BMP concentration, which is available in the ventrolateral part (V) of the embryo (as shown). Under these conditions, Collinear opening of chromatin and the Hox-Hox interaction posterior induction (PI) [36][37][38][39][40], which is necessary for TC, also occur as do Wnt and Cdx inputs into Hox1 genes and Hoxc6, respectively [41]. A thin segment at the right side of the embryo has a blue background (shown in detail for the embryos at the right side of the figure).…”

A Tribute to Lewis Wolpert on the 50th Anniversary of the Publication of His Paper ‘Positional Information and the Spatial Pattern of Differentiation’. Evidence for a Timing Mechanism for Setting Up the Vertebrate Anterior-Posterior (A-P) Axis

“…The (extensive) evidence for this mechanism is given in three recent reviews: Deschamps and Duboule, 2017, Durston, 2019cand Durston, 2019d. Space prohibits repeating it here again; Please note that many of the features of this mechanism are also relevant for limb P-D patterning: namely, retinoids, FGF, Hox genes, chromatin histone acetylation, collinear opening of Hox cluster chromatin, Hox-Hox interactions, action of different morphogens at different stages..…”

Some Questions and Answers About the Role of <em>Hox</em> Temporal Collinearity in Vertebrate Axial Patterning

“…The following analysis examines, answers and draws conclusions from some of the questions raised. I centre it around comparing and contrasting the two recent models (Durston and Zhu, 2015, Durston, 2015, 2019c Deschamps and Duboule, 2017 (dedu)).Conclusion: An analysis of the important facts around Hox collinearity and timing in axial patterning is required because this is a complex subject where there has been too little discussion . This article strives to make sense of the literature.…”