Mammalian Embryo: Hox Genes

Tara B Alexander, Stowers Institute for Medical Research, Kansas, Missouri, USA
Robb Krumlauf, Stowers Institute for Medical Research, Kansas, Missouri, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0000740.pub2

Hox genes are evolutionarily conserved transcription factors that play important roles in establishing the basic body plan of animals. Mammals have 39 Hox genes clustered into four chromosomal complexes. This gene family regulates the regional character and patterning of diverse structures along the anterior–posterior (A/P) axis of the embryo. Nested patterns of Hox gene expression generate a Hox combinatorial protein code that orchestrates the morphogenesis of structures in the nervous system, axial skeleton, limbs, intestine and many other tissues. In light of their key role in regulating morphogenesis across animal species, modulation of Hox expression or function over the course of evolution is believed to have been important in generating diversity.

Key concepts:

  • Axial patterning is the process that generates different regional characteristics during the development of a tissue, such as the nervous system or skeleton.
  • Hox genes encode a family of transcription factors that regulate the identity of structures along the anterior–posterior axis of embryos.
  • Colinearity is the correlation between the order of Hox genes along a chromosome and their expression along the axis of an embryo.
  • The collection of Hox proteins expressed in a region provides a combinatorial code for specifying diversity.
  • Posterior prevalence is a model for explaining why some Hox proteins dominate over others when they are coexpressed.
  • Selector genes control the identity of a tissue.
  • Homeotic transformation is the conversion of one structure into another due to loss or gain of selector gene activity.
  • Segmentation subdivides a developing tissue, such as the hindbrain or skeleton, into repeating units that ultimately generate different structures along an axis.
  • Subfunctionalization is the partitioning of function and regulation between duplicated genes compared with the ancestral gene.
  • Changes in Hox expression or function may be important for generating differences in structures during evolution of vertebrates.
  • Cooption refers to the redeployment or coupling of a common molecular pathway to multiple patterning processes.

Keywords: homeobox; axial patterning; gene regulation; transcription factors; embryogenesis

Figure 1. Schematic representation of the mammalian Hox gene clusters. The four mammalian clusters, named A to D, arose by two rounds of whole genome duplications from a single Hox cluster that is hypothesized to have closely resembled the Hox cluster of the invertebrate chordate amphioxus. The similarity in structure and function of the mammalian and Drosophila complexes supports the view that a Hox cluster composed of Anterior, Group3, Central and Posterior classes of Hox genes existed before the divergence of the protostome and deuterstome lineages. The mammalian Hox genes are arranged in the same transcriptional orientation, so the cluster is said to have a 3¢–5¢ polarity. 3¢ Hox genes are expressed first, followed by the expression of progressively more 5¢ genes, a phenomenon referred to as temporal colinearity. Mammalian Hox gene expression extends from the posterior of the embryo to an anterior boundary characteristic for each Hox gene. Spatial colinearity describes the correlation between the axial level of this anterior boundary and Hox gene order within the cluster; the further 5¢ a gene is located within the cluster the more posterior is its anterior expression limit.
Figure 2. Regulatory subfunctionalization. In this example, the ancestral gene is regulated by 3 discrete cis-elements (red, yellow and blue). After duplication the gene copies will be functionally redundant. The most likely outcome is the loss of one of the gene copies to deleterious mutations. However, both gene copies may be retained to perform all of the functions of the ancestral gene if complementary, loss-of-subfunction mutations (white circles) occur in the modular enhancers.
Figure 3. Hox gene expression in the developing hindbrain. Anterior members from the HoxA and B clusters are expressed with overlapping domains along the neuraxis with anterior limits of expression in the hindbrain and distinct domains of higher expression. Some of the upstream regulators of Hox genes in the hindbrain, such as Kreisler and Krox20, are also expressed in a segmental pattern. r1–r8, rhombomeres; sc, spinal cord and ov, otic vesicle.
Figure 4. Hox gene expression in the paraxial mesoderm. Hox gene expression is turned on in the epiblast lateral to the primitive streak (ps) in a temporally colinear sequence. The orange square represents the subset that will contribute to the paraxial mesoderm. Cells that ingress through the primitive streak at a level just posterior to the node (n) will join the posterior presomitic mesoderm (PSM). Somites form sequentially at the anterior PSM (dotted line). Thus, anterior somites are formed by cells entering the primitive streak early and expressing a more 3’ subset of Hox genes. Arrowheads indicate direction of movement of epiblast cells. Arrows indicate direction of movement of cell after they have ingressed through the primitive streak. n, node and ps, primitive streak.
Figure 5. Hox gene expression in the developing limb. In the early limb bud, Hox gene expression is temporally and spatially colinear. In the late phase, Hox gene expression is quantitatively colinear in the region forming the digits. Only Hoxd13 is expressed in the presumptive thumb domain (*).
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Genes, Molecules and Cellular Processes | Evolution of Coding and Functional Modules
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Article Title: Mammalian Embryo: Hox Genes
 
How to Cite close
Alexander, Tara B, and Krumlauf, Robb(Sep 2009) Mammalian Embryo: Hox Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000740.pub2]