Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis

Abstract

Investigating regulation and function of the Hox genes, key regulators of positional identity in the embryo, opened a new vista in developmental biology. One of their most striking features is collinearity: the temporal and spatial orders of expression of these clustered genes each match their 3’ to 5’ order on the chromosome. Despite recent progress, the mechanisms underlying collinearity are not understood. Here we show that ectopic expression of 4 different single Hox genes predictably induces and represses expression of others, leading to development of different predictable specific sections of the body axis. We use ectopic expression in wild-type and noggin—dorsalised (Hox-free) Xenopus embryos, to show that two Hox-Hox interactions are important. Posterior induction (induction of posterior Hox genes by anterior ones: PI), drives Hox temporal collinearity (Hox timer), which itself drives anteroposterior (A-P) patterning. Posterior prevalence (repression of anterior Hox genes by posterior ones: PP) is important in translating temporal to spatial collinearity. We thus demonstrate for the first time that two collinear Hox interactions are important for vertebrate axial patterning. These findings considerably extend and clarify earlier work suggesting the existence and importance of PP and PI, and provide a major new insight into genesis of the body axis.

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

“…Posterior induction (PI) is likely to be the basis of temporal collinearity (Faiella et al, 1994;Hooiveld et al, 1999;McNulty et al, 2005;Zhu et al, 2017aZhu et al, , 2017b. This regulatory mechanism works sequentially.…”

“…The evidence that these three types of Hox-Hox interactions mediate Hox collinearities and TST comes principally from gain and loss of function experiments, especially from the cascade phenotypes ( Figure 2) that are sometimes seen (Faiella et al, 1994;Hooiveld et al, 1999;McNulty et al, 2005;Zhu et al, 2017aZhu et al, , 2017b.…”

“…In the trunk-tail part of the axis, these determinants are the Hox genes (Figure 3a). The anterior boundary for the earliest Hoxc6 expression is always at the cervical-thoracic transition in PM (Burke et al, 1995;Gaunt, 2000;McIntyre et al, 2007;Zhu et al, 2017aZhu et al, , 2017b. The anterior boundary for Hoxb4 is close to the boundary between posterior head and neck and the occipital/cervical transition in the PM.…”

“…The head and tail of the A-P timer are close together because of their representation on a clock face. No statement about molecular identities is intended 3.3.1 | The induction of expression of more 5 0 posterior Hox genes by more 3 0 anterior Hox genesreferred to as posterior induction (PI) Posterior induction (PI) is likely to be the basis of temporal collinearity (Faiella et al, 1994;Hooiveld et al, 1999;McNulty et al, 2005;Zhu et al, 2017aZhu et al, , 2017b. This regulatory mechanism works sequentially.…”

Hoxc6 loss of function truncates the main body axis in Xenopus

“…While at first sight this may seem contradictory to posterior prevalence, it is compatible with and explainable by our recent result that posterior prevalence starts to exert its influence from st.15 in paraxial mesoderm. 7 What is important is that results in Fig. 1D and E suggest hoxc6 LOF cuts off the temporal sequence of Hox expression and stops the Hox timer.…”