Vertical Signalling Involves Transmission of Hox Information from Gastrula Mesoderm to Neurectoderm

Abstract

Development and patterning of neural tissue in the vertebrate embryo involves a set of molecules and processes whose relationships are not fully understood. Classical embryology revealed a remarkable phenomenon known as vertical signalling, a gastrulation stage mechanism that copies anterior-posterior positional information from mesoderm to prospective neural tissue. Vertical signalling mediates unambiguous copying of complex information from one tissue layer to another. In this study, we report an investigation of this process in recombinates of mesoderm and ectoderm from gastrulae of Xenopus laevis. Our results show that copying of positional information involves non cell autonomous autoregulation of particular Hox genes whose expression is copied from mesoderm to neurectoderm in the gastrula. Furthermore, this information sharing mechanism involves unconventional translocation of the homeoproteins themselves. This conserved primitive mechanism has been known for three decades but has only recently been put into any developmental context. It provides a simple, robust way to pattern the neurectoderm using the Hox pattern already present in the mesoderm during gastrulation. We suggest that this mechanism was selected during evolution to enable unambiguous copying of rather complex information from cell to cell and that it is a key part of the original ancestral mechanism mediating axial patterning by the highly conserved Hox genes.

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

“…We conclude that sequentially repeated interactions between the two embryonic parts lead to successive small populations of cells being fixed at sequential space/time points. The fixed identity populations are in the dorsal paraxial mesoderm, which also contains and/or generates the timer population in presomitic mesoderm, and which is derived from NO mesoderm after convergence extension movements during gastrulation, as well as in dorsal neurectoderm, due to copying of identities from paraxial mesoderm to neurectoderm during neural transformation (Bardine et al, 2014;Mangold, 1933;Nieuwkoop, 1952). This TST mechanism was first demonstrated for the genesis of Hox pattern zones in the neck and more posterior parts of the body axis during gastrulation and later stages in Xenopus (Wacker, Jansen, et al, 2004).…”

A time space translation hypothesis for vertebrate axial patterning

“…This function involves precise copying of positional information from NOM mesoderm (vertical signalling) exactly as predicted by Mangold [43]. The mechanism involves very specific non cell autonomous autoregulation of individual Hox genes such that their expression in NOM mesoderm is copied to neighbouring neurectoderm (Text Box 3) [44].…”

“…S3C [17].Blocking the function of a single Hox gene in NOM prevents induction of the same Hox gene in NE in a wrap recombinate. This indicates that a function of NOM is to posteriorise NE via non cell autonomous autoregulation of individual Hox genes [44].…”

“…There are also functionality experiments that show that Hox genes are involved in generating positional values and Hox spatial collinearity in the trunk and that the Hox genes interact [5]. There is also evidence that transfer of positional information from NOM mesoderm to neurectoderm during TST (=vertical signalling) [43] is mediated by specific non cell autonomous autoregulation of individual Hox genes [44]. The Hox genes thus appear to be part of the core mechanism for TST.…”

“…Knocking down the entire first Hox paralogue group (Hox 1) knocks down most or all of the spatially collinear Hox sequence (At least back to Hox9), indicating that Hox1 functionality is also involved in this process [5]. A second indication of the importance of Hox function is that knocking down individual Hox genes in NOM mesoderm specifically prevents vertical signalling: copying of the expression of the same Hox genes for NOM to neurectoderm (NE) in 'wrap' recombinates, which copies the same process in vivo where vertical signalling is part of TST [44]. These findings give a clue to the mechanism of TST (below).…”