The dorsal-ventral axis and why some organisms are upside-down

By Heiloi Yip

Developmental biologists have long since been investigating how bilaterian organisms are able to generate complex three-dimensional shapes from a small sphere of cells that some call the embryo. Clearly, a massive amount of coordination is required between each cell to generate such shapes. For example, the cells need to know where they are positioned relative to the embryo, so that they may divide and differentiate into the correct organ at the correct location. The main way cells receive their positional information is by using three cardinal axes within the embryo. These axes are usually established by signaling molecules and are formed early on during embryonic development. The dorsal-ventral axis essentially differentiates the back from the belly, and this developmental system has a very intriguing evolutionary history. 

In vertebrates such as ourselves, two signaling molecules are involved in establishing the dorsal-ventral axis. One of these is the bone morphogenetic protein 4 (BMP4) which signals to cells to develop into features that would be expected at the ventral side. Another molecule, Chordin, signals cells to develop dorsal organs. BMP4 is expressed throughout the embryo, while Chordin expression is controlled by the blastula lip during gastrulation, resulting in Chordin expression being limited to cells at one side of the embryo. Wherever Chordin is present, it acts antagonistically to BMP4 signaling, thus limiting BMP4 expression to the other side of the embryo. The result is two opposing poles of signaling molecules, forming an axis across the embryo. The cells of the embryo will interpret the levels of Chordin/BMP4 they are being exposed to, and thus differentiate into the appropriate organ according to the axis.  

Scientists have been able to extensively study these signaling molecules thanks to experimentation on model organisms such as frog embryos (Xenopus laevis). As expected, the frog embryo uses the same Chordin-BMP4 system common to vertebrates. Homologues of these two molecules have been found in a distantly related model organism, the fruit fly (Drosophila melanogaster). Here, short gastrulation (Sog) is the homologous equivalent of vertebrate Chordin, while Decapentaplegic (Dpp) is homologous to BMP4. Sog antagonises expression of Dpp, the same interaction Chordin has with BMP4.  However, there is a catch: the roles of Sog and Dpp are swapped in fruit flies! Dpp signals for dorsal development, while Sog is the ventral signal. The homologous nature between Sog and Chordin, despite their seemingly opposite roles, can be shown by injecting Sog mRNA into a frog embryo, whereby the resulting embryo gains an extra blastula lip where the mRNA was injected (Holley et al., 1995). The reversal of the dorsal-ventral axis is not as simple as swapping molecules, for there are anatomical consequences that can be spotted. One of these consequences is the position of the nervous system relative to other organs. In the frog embryo, the nerve chord develops dorsally, whereas the fly nerve chord is located ventrally. This suggests Chordin/Sog is responsible for development of the nervous system, arising in nerve chords wherever the molecules end up being expressed in the embryo. 

While the Chordin-BMP4 system is widely used among vertebrates, the Sog-Dpp system is common to protostome organisms, which include the arthropods (such as fruit flies) (ScienceBlogs, 2006). This begs the question of which arrangement of the dorsal-ventral axis is the ancestral state. A study on hemichordates, a closely related group to the vertebrates, reveals they have their dorsal-ventral axis arranged similarly to protostomes, thus proving that the Sog-Dpp system represents the ancestral state. Therefore, it is the ancestors of vertebrates that inverted the axis sometime during its evolution! (Gerhart, Lowe & Kirschner, 2005)

The conclusion to be drawn from these findings is that the system for establishing the dorsal-ventral axis evolved a long time ago and remains highly conserved among all bilaterian organisms. However, the interpretation of signaling molecules appears to be more flexible, as evident by the Chordin-BMP4 system in vertebrates. At one point during the evolution of the vertebrates, they have swapped the roles of the pair of signaling molecules that would be named Chordin and BMP4, resulting in a whole lineage of animals with an inverted dorsal-ventral axis.  

References:

Gerhart, J., Lowe, C. & Kirschner, M. (2005) Hemichordates and the origin of chordates. Current Opinion in Genetics & Development. 15 (4), 461-467. Available from doi: 10.1016/j.gde.2005.06.004  

Holley, S., Jackson, P., Sasai, Y., Lu, B., Robertis, E., Hoffmann, F. & Ferguson, E. (1995) A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature. 376 (6537), 249-253. Available from: doi: 10.1038/376249a0 

ScienceBlogs. (2006) Hemichordate evo-devo. Available from: https://scienceblogs.com/pharyngula/2006/01/12/hemichordate-evodevo [Accessed 22 February 2021]. 

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