XMeis3 Is Necessary for Mesodermal Hox Gene Expression and Function

Paul M J In Der Rieden,Hans J Jansen,Antony J Durston,Christoph Winkler

doi:10.1371/journal.pone.0018010

Abstract

Hox transcription factors provide positional information during patterning of the anteroposterior axis. Hox transcription factors can co-operatively bind with PBC-class co-factors, enhancing specificity and affinity for their appropriate binding sites. The nuclear localisation of these co-factors is regulated by the Meis-class of homeodomain proteins. During development of the zebrafish hindbrain, Meis3 has previously been shown to synergise with Hoxb1 in the autoregulation of Hoxb1. In Xenopus XMeis3 posteriorises the embryo upon ectopic expression. Recently, an early temporally collinear expression sequence of Hox genes was detected in Xenopus gastrula mesoderm (see intro. P3). There is evidence that this sequence sets up the embryo's later axial Hox expression pattern by time-space translation. We investigated whether XMeis3 is involved in regulation of this early mesodermal Hox gene expression. Here, we present evidence that XMeis3 is necessary for expression of Hoxd1, Hoxb4 and Hoxc6 in mesoderm during gastrulation. In addition, we show that XMeis3 function is necessary for the progression of gastrulation. Finally, we present evidence for synergy between XMeis3 and Hoxd1 in Hoxd1 autoregulation in mesoderm during gastrulation.

Highlights

During the development of most animal species studied, Hox transcription factors specify positional information along the anterior - posterior axis [1,2,3,4,5]
To determine whether XMeis3 is co-expressed with Hox genes in the mesoderm of gastrula embryos, whole mount in situ hybridisation was performed for XMeis3, Hoxd1, Hoxb4, and Hoxc6 (Fig. 1)
We made four main findings which relate to the role of the early gastrula non organiser mesoderm which has recently been shown to be very important in early embryonic patterning [40,41]

Summary

Introduction

During the development of most animal species studied, Hox transcription factors specify positional information along the anterior - posterior axis [1,2,3,4,5]. Pbx/Exd family members are part of a particular subfamily of the homeodomain containing proteins, namely the TALE-class. This class is characterised by having a three amino acid loop extension between the first and second helices of the homeodomain [11]. When Hox proteins bind to DNA cooperatively with a Pbx/Exd family member, the main protein-protein interaction consists of binding of the hexapeptide motif of the Hox protein to a pocket formed by the atypical homeodomain of PBC family members [13,14,15] This pocket is composed of the three amino acid loop extension of the PBC homeodomain, residues in the third helix of the homeodomain, and a residue in the C-terminal helix of PBC homeodomains [15]. The nuclear localisation of Pbx/Exd proteins is controlled by competing nuclear import and export signals [16]

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Discussion

Conclusion