Segmentation is an important concept in embryology. Early animals, for example nematodes or very early insects, are built around a repeating pattern. The segments of later insects are also repeated, but some have become specialised with modified legs, mouth parts or wings. The evolution of these changes is recorded, to an extent, within the genes responsible for early organisation and patterning of the embryos of these animals.
A common insect used for investigating and discussing embryol-gmentation in particular, is the fruit fly, also known as rosophila melanogaster.
The cells of the Drosophila embryo are initially organised along a craniocaudal axis by a morphogen gradient (see Chapter 3 for a similar example of a morphogen gradient). This is followed by the expression of different genes by the cells of the embryo, but only in particular bands along its length. These are gap genes (Figure 21.1). This banded pattern of gene expression becomes more pro- nounced when pair rule genes are expressed in alternating stripes by the cells of the embryo (Figure 21.2). This level of organisation is pushed even further by the expression of segment polarity genes within those segments (Figure 21.3).
Now that the embryo is organised into similar segments, the cells of each segment need further information from which morphogenesis will shape the appropriate structures for each segment (e.g. a wing, or a leg).
Hox genes are genes that share a similar homeobox domain of 180 base pairs, which encodes for a sequence of 60 amino acids. The term ‘homeobox’ refers to the sequence of base pairs, and the term ‘homeodomain’ refers to the section of protein that corre- sponds to the homeobox. The homeodomain is highly conserved between genes and between species, with small differences.
Hox genes are involved in the very early specification of the segments of the embryo, from which the development of morphologically different segments can occur. They are expressed in bands along the length of the embryo (Figure 21.4), and in vertebrates there are multiple, overlapping, similar sets of Hox genes (clusters) that gives some redundancy and more complex organisation than possible in the development of the fly. The Hox genes of Drosophila do not have this redundancy, so knocking out Hox genes gives profound effects. A common example is the Antennapedia mutant, in which the fly develops legs where its antennae would normally form (Figure 21.5). The Hox gene that would normally specify this segment is lost, the pattern is broken and the segment is re‐specified.
Hox genes are found together on the same chromosome, lined up. Interestingly, they are lined up in their order of expression along the craniocaudal axis. In humans the 4 clusters of Hox genes are found on 4 different chromosomes.
The Hox proteins that result from Hox gene expression are DNA binding transcription factors, able to switch on cascades of genes. The homeodomain is the DNA binding region of the protein.
All of this organisation leads to the formation of visible early segmentation patterns such as the somites (see Chapter 22), from which adult segmented structures develop. In humans and other vertebrates the segmentation pattern can be seen in the vertebrae, ribs, muscles and nervous innervation patterns (see Figure 22.5). These segments form sequentially, one pair after another.
Before somites form, cells of the presomitic mesoderm display oscillating patterns of gene expression, meaning the expression of genes switches on, off and on again with time. This rhythmic expression of genes of the Notch pathways and their targets is known as the segmentation clock. You can think of each cell hav- ing its own clock and its own time.
A morphogen gradient of fibroblast growth factor (FGF) and Wnt is secreted by cells at the tail end of the presomitic meso- derm. You might call the edge of this morphogen gradient the wavefront.
As cells at the caudal end of the presomitic mesoderm proliferate and the tail grows, the cells producing FGF and Wnt move further away from the head and from other presomitic mesoderm cells. Some cells of the presomitic mesoderm no longer feel the effects of FGF and Wnt as the wavefront moves away from them, and they begin to form somites.
The band of cells that leave the wavefront will either form the cranial end or the caudal end of the somite depending upon the time of their segmentation clock at the point at which they leave the wavefront. The temporal nature of the segmentation clock is translated into the spatial arrangement of somites via these mechanisms (Figure 21.6).
How the segmentation clock works is still not entirely under-stood, but the understanding of these mechanisms has developed remarkably over the last 15 years.
Through the embryology of segmentation we can see the path of evolution and links between vastly different animals, existing now and in prehistory, and the mechanisms behind anatomical similari- ties amongst vertebrates. The giraffe, for example, has 7 cervical vertebrae in its very long neck, just as we do in our much shorter variant. While segmentation is clearly apparent in the bony structures of adult anatomy, the embryology here helps us understand the arrangement of many of the soft tissues too.
Minor errors in segmentation can produce vertebral and intervertebral defects. A wedge‐shaped hemivertebra may form, causing a form of congenital scoliosis that worsens as the hemivertebra grows. A number of variations have been documented. Other vertebrae may be fused completely, just laterally, posteriorly or anteriorly, if the intervertebral space fails to form completely osis or lordosis. Other developmental processes ay also cause these deformities.