Hox Genes: Embryonic Development


Hox genes encode a family of transcription factors responsible for the establishment of the animal body plan. Their organisation in genomic clusters is conserved during evolution and is instrumental in defining the domain of activity of each gene in the embryo: the place and time of Hox gene expression is dictated by the position of each gene within the cluster. A unique set of Hox genes is active at each axial level along the embryonic anterior to posterior axis. These diverse complements of Hox proteins determine morphological identities by controlling the transcription of specific target genes. Changes in Hox genes number, expression and function likely participated in morphological diversification during animal evolution.

Key Concepts

  • Hox genes determine the identity of structures along the anterior–posterior embryonic axis.
  • Hox genes are widely conserved among animal species and are organised in genomic clusters.
  • Colinearity is the correspondence between the order of Hox genes within the cluster and their time and place of expression along the embryonic axis.
  • Loss or gain of function of Hox genes lead to homeosis, the morphological transformation of a body structure into another one.
  • Hox proteins regulate specific sets of target genes by interacting with dedicated cofactors.
  • Hox gene regulation integrates multiple inputs via complex sets of local and long‐range cis‐acting regulatory elements.
  • Chromatin modifiers of the Polycomb and Trithorax families are critical in controlling the onset and maintenance of Hox gene transcription.
  • Changes in Hox gene expression and function accompanied major morphological transitions during animal evolution.

Keywords: gene clusters; homeosis; homeobox; homeodomain; transcription factors; patterning; gene regulation; enhancer; embryogenesis; morphological evolution

Figure 1. Functional organisation of Hox gene clusers. (a) A Drosophila embryo with anterior to the left. (b) Hox complexes of Drosophila and human. (c) Expression patterns of Hox paralogy groups 1, 4 and 7 in the anterior central nervous system, in the mouse. Gene order is conserved between insects and mammals (arrows indicate gene homology). The expression territories of Hox genes reflect their order in the complexes (gene expression domains are depicted with a colour code). The collinear arrangement of Hox genes in the cluster is indicated relative to spatial expression (anterior/rostral vs posterior/caudal), timing of expression (early vs late) and retinoic acid (RA) sensitivity (high vs low).
Figure 2. Control of target genes transcription by Hox proteins. (a) Hox proteins have similar DNA binding properties and display low affinity and specificity (left). Heterodimerisation with cofactors (such as Exd) alters binding specificity and allows selection of unique binding sites for each Hox–Exd dimer (right). (b) Distinct Hox proteins can bind the same regulatory element in different embryonic territories. This can lead to either transcriptional activation (left) or repression (right).
Figure 3. Transcriptional regulation of vertebrate Hox clusters. (a) During early vertebrate development, Hox clusters are initially repressed by Polycomb (PcG)‐dependent chromatin modifications (H3K27me3, red). Along with the extension of the A–P axis, H3K27me3 is progressively erased and replaced by Trithorax (TrxG)‐dependent H3K4me3 (green). This transition parallels the progressive transcriptional activation of Hox genes, under the control of multiple enhancers embedded within the gene cluster (blue ovals). (b) Long‐range regulation of Hox clusters in secondary axes. In addition to their evolutionary conserved expression along the A–P axis, vertebrate Hox clusters acquired novel expression territories involved in the patterning of diverse structures or organs, such as the limbs or external genitalia. In these tissues, Hox genes are regulated by long‐range enhancers located outside the gene clusters. Each of these distinct expression specificities (coloured arrows) usually depends on multiple and partially redundant enhancer elements (ovals).


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Further Reading

Casaca A, Santos AC and Mallo M (2014) Controlling Hox gene expression and activity to build the vertebrate axial skeleton. Developmental Dynamics 243: 24–36.

Duboule D (2007) The rise and fall of Hox gene clusters. Development 134: 2549–2560.

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Quinonez SC and Innis JW (2014) Human HOX gene disorders. Molecular Genetics and Metabolism 111: 4–15.

Zákány J and Duboule D (2007) The role of Hox genes during vertebrate limb development. Current Opinion in Genetics and Development 17: 359–366.

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Montavon, Thomas(Jun 2015) Hox Genes: Embryonic Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005046.pub2]