Controlling Hox gene expression and activity to build the vertebrate axial skeleton

Abstract

It has long been known that Hox genes are central players in patterning the vertebrate axial skeleton. Extensive genetic studies in the mouse have revealed that the combinatorial activity of Hox genes along the anterior-posterior body axis specifies different vertebral identities. In addition, Hox genes were instrumental for the evolutionary diversification of the vertebrate body plan. In this review, we focus on fundamental questions regarding the intricate mechanisms controlling Hox gene activity. In particular, we discuss the functional relevance of the precise timing of Hox gene activation in the embryo. Moreover, we provide insight into the epigenetic regulatory mechanisms that are likely to control this process and are responsible for the maintenance of spatially restricted Hox expression domains throughout embryonic development. We also analyze how specific features of each Hox protein may contribute to the functional diversity of Hox family. Altogether, the work reviewed here further supports the notion that the Hox program is far more complex than initially assumed. Exciting new findings will surely emerge in the years ahead. Developmental Dynamics 243:24-36,

MOZ and BMI1 play opposing roles during Hox gene activation in ES cells and in body segment identity specification in vivo

“…In agreement with this interpretation of our data, there is increasing evidence that the timely activation of Hox genes is critical for proper anterior-posterior patterning (see review by ref. 40). For instance, deletion of the Hoxc8 enhancer (41), or deletion of the Hoxd10 enhancer (42), leads to a temporal delay in activation of the respective Hox gene and anterior shifts in body segment identity.…”

Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity

“…However, they produce skeletal elements with unique anatomical features characteristic of their position along the anteriorposterior body axis. This regional differentiation of somites is to a large extent under the control of Hox genes (Pearson et al, 2005;Mallo et al, 2010;Casaca et al, 2014). In mammals, the Hox gene family is composed of 39 members distributed in four gene clusters resulting from two consecutive duplications of an ancestral cluster.…”

“…This led to the classification of Hox genes into 13 groups, normally known as paralog groups (PGs) (Prince, 2002;Duboule, 2007). A variety of genetic studies revealed that Hox proteins have a high degree of functional specificity, often shared by the different members of the same PG (Casaca et al, 2014). It is thought that morphological diversity in the axial skeleton results from the combined activities provided by the different Hox PGs (Mallo et al, 2009;Wellik, 2009).…”

“…It is clear that Hox functional specificity is largely encoded in non-HD parts of the protein Potter, 2001, 2002;Guerreiro et al, 2012), either in the form of intrinsic functional activities or by their ability to recruit additional factors (Mann et al, 2009;Casaca et al, 2014). Understanding the patterning activity of these Hox proteins thus requires the identification and characterization of the molecular signatures responsible for their functional specificity.…”

Whole Genome Sequencing Identifies a Missense Mutation in HES7 Associated with Short Tails in Asian Domestic Cats

“…Understanding the genetic causes of intraspecific tail length polymorphism would be one essential step toward elucidating the mechanisms underlying the development and evolution of tails. In laboratory mice, genetic studies of axial skeleton development have identified multiple genes and mutations involved in caudal vertebra development that have pleiotropic effects on fertility, somitogenesis, and meiotic recombination, thus shedding light on vertebrate evolution2345. However, given the tremendous variety of tail morphology found in animals, mice alone may not be able to capture the full spectrum of the evolutionary diversity of mammalian tails.…”