Organizing Axes in Time and Space; 25 Years of Colinear Tinkering

Abstract

During vertebrate development, clustered genes from the Hox family of transcription factors are activated in a precise temporal and spatial sequence that follows their chromosomal order (the "Hox clock"). Recent advances in the knowledge of the underlying mechanisms reveal that the embryo uses a variety of strategies to implement this colinear process, depending on both the type and the evolutionary history of axial structures. The search for a universal mechanism has likely hampered our understanding of this enigmatic phenomenon, which may be caused by various and unrelated regulatory processes, as long as the final distribution of proteins (the HOX code) is preserved.

Developmental expression patterns of cuticular protein genes with the R&R Consensus from Anopheles gambiae

“…In contrast, genes in the human β-globin cluster are lined in the order of temporal timing of expression (Jane and Cunningham, 1996;Li et al, 2006). Several models to explain the regulatory mechanism of this concerted expression have been proposed (Kmita and Duboule, 2003;Li et al, 2006;Negre and Ruiz, 2007). With the CPR genes, there was no coordinated regulation of genes in tandem arrays except for the subsets of some RR-2 genes that are found in sequence clusters.…”

Epigenetic regulations in hematopoietic Hox code

“…Then a progressive 3 0 -5 0 change in high-order chromatin structure, which is manifested as the movement outside of chromatin territories, is necessary to allow for the programmed expression of genes along the cluster. In parallel with Hox colinearity, a sequential opening of chromatin, starting at the 3 0 end of a cluster and moving successively toward 5 0 , leads to the release of silencing first at the 3 0 end, and sequentially, allowing the expression of more 5 0 genes (Roelen et al, 2002;Kmita and Duboule, 2003;Duboule and Deschamps, 2004). In hematopoietic cells, menin-MLL complexes modulate the chromatin accessibility to upstream regulators of Hox genes (Figure 1a).…”

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

“…Although most analyses have been performed in the forelimb (suggesting that the data we present below have been established for the forelimb), they undoubtedly apply to the hindlimb as well. An extensive discussion of this work is beyond the scope of this review, and the reader is referred to recent reviews (Kmita and Duboule, 2003;Freitas and Cohn, 2006). However, major rules are emerging that are presented below.…”