T-box genes in early embryogenesis

Abstract

The T-box gene family, encoding related DNA-binding transcriptional regulators, plays an essential role in controlling many aspects of embryogenesis in a wide variety of organisms. The T-box genes exhibit diverse patterns of spatial and temporal expression in the developing embryo, and both genetic and molecular embryological studies have demonstrated their importance in regulating cell fate decisions that establish the early body plan, and in later processes underlying organogenesis. Despite these studies, little is known of either the regulation of the T-box genes or the identities of their transcriptional targets. The aim of this review is to examine the diverse yet conserved roles of several T-box genes in regulating early patterning in chordates and to discuss possible mechanisms through which this functional diversity might arise. Developmental Dynamics 229:201-218, 2004.

Fig. 1

Brachyury is expressed in, and required for, posterior and axial mesoderm. A: Whole-mount in situ hybridization of an embryonic day 8 mouse embryo contained within its extra-embryonic tissue. Note strong expression of Brachyury in the primitive streak, the future posterior region of the embryo, and in the prospective notochord cells, along the ventral side of the embryo. Anterior is shown to the left, posterior to the right. B: Wild-type (left) and Brachyury homozygous mutant (right) littermates after whole-mount TUNEL staining to visualize programmed cell death. C,D: Posterior tissue shown at higher magnification of the wild-type embryo (C) and homozygous mutant (D).

Fig. 2

The inducing activities of T-box genes in Xenopus animal cap assays. Explants from the animal pole (“animal cap”), marginal zone, and vegetal pole differentiate into ectodermal, mesodermal, and endodermal cell types when cultured in isolation. Misexpression of T-box genes in animal caps induces expression of specific subsets of mesodermal (red) and endodermal (green) genes and promotes differentiation into corresponding cell types.

Fig. 3

T-box genes regulate axial and paraxial mesoderm development in zebrafish. a: Diagrammatic representation of T-box gene expression patterns in the epiblast and hypoblast of zebrafish gastrulae. Dorsal views are shown. Expression of spadetail (spt; blue) and tbx6 (tbx6; red) overlaps in the segmental plate (S; presomitic paraxial mesoderm) and in the tail bud (T). no tail (ntl; green) is expressed in the notochord (N) and in the tail bud, where it is coexpressed with spadetail and tbx6. Note the spadetail-expressing adaxial cells (arrowhead, see Griffin et al., 1998). b: Genetic pathways governing cell fate in the axial mesoderm (i.e., notochord) and paraxial mesoderm of the zebrafish trunk and tail.

Fig. 4

Sequence alignment of the T-domains of Xenopus Xbra, Eomesodermin (Eomes), and VegT. Regions of sequence identity are shown for each protein (upper case), based on comparisons between the Xenopus proteins and their orthologues in zebrafish (Xbra, VegT), mouse (Xbra, Eomes), and human (Eomes). Regions of sequence identity between the three T-domains are highlighted in yellow. Amino acid residue K149 of Xbra, contributing to functional specificity (Conlon et al., 2001), is also highlighted (in blue) along with the corresponding residues in Eomesodermin and VegT.