Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Abstract

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with large-scale regulation and chromatin structure during the development of both axial and limb patterns. We further discuss how this sequential transcriptional activation marks embryonic stem cell-like axial progenitors in mammals and, consequently, how a temporal genetic system is further translated into spatial coordinates via the fate of these progenitors. In this context, we argue the benefit and necessity of implementing this unique mechanism as well as the difficulty in evolving an alternative strategy to deliver this critical positional information.

Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis

“…property of collinearity also applies to the relative response of Hox genes to signaling pathways such as RA, FGFs, and Wnts (Bel-Vialar, Itasaki, & Krumlauf, 2002;Boncinelli, Simeone, Acampora, & Mavilio, 1991;Deschamps & Duboule, 2017;Neijts et al, 2016;Papalopulu, Lovell-Badge, et al, 1991;Pownall, Tucker, Slack, & Isaacs, 1996).…”

“…This is followed by the anterior spreading of their expression domains in a nonlineage dependent fashion (Deschamps & Wijgerde, 1993). Once the expression domains reach cells anterior and lateral to the node (N), their expression pattern is clonally transmitted in the progenitors of the neurectoderm (NE), and paraxial mesoderm (PM; It is during the initiation phase that there is co-linear activation of the Hox genes, such that the 3 0 located Hox genes are activated before the 5 0 members of the cluster (Deschamps & Duboule, 2017;Iimura & Pourquie, 2006). This phase is marked by changes in the 3D topology of the complexes (Chambeyron & Bickmore, 2004;Morey, Da Silva, Perry, & Bickmore, 2007;Neijts et al, 2016;Noordermeer et al, 2011) and the rapid removal of H3K27me3 marks from the 3 0 end of the complexes (De Kumar et al, 2015;Mazzoni et al, 2013).…”

The Mobilome of Reptiles: Evolution, Structure, and Function

“…There is no reason to believe that the close examination of reptile genomes would not yield a trove of domesticated TEs. Indeed, the accumulation of TEs in the Hox clusters of reptiles [Di-Poï et al, 2009, which contrast with the extreme structural stability of those clusters in other vertebrates [Deschamps and Duboule, 2017] 29 TE insertions could have had an impact on the morphological diversity of squamates [Di-Poï et al, 2010] as well as the rate of speciation in anoles [Feiner, 2016]. Much work remains to be done to confirm a functional role of those insertions in the evolution of phenotypes.…”

Evolution of vertebrate spinal cord patterning

“…Establishment and maintenance of Hox gene expression in the spinal cord is a complex affair, involving regulation by multiple external signals, by interactions between Hox genes, and by change in chromatin state through developmental time. There is insufficient space here to detail all of these, and the reader is referred to a recent review for a detailed exploration of these issues . However, some key generalizations can be extracted (Figure ).…”