15) The Wnt pathway in evolutionary developmental biology (by Theodor Zbinden)

There are a variation of important concepts in the evo devo field; one of them is modularity.  For an evolutionary biologist modularity means a module as a morphologic component, subunit or extremities of the entire organism.  The module represents a basic component of the organism.  However for a developmental biologist the term means some combination of lower level components like a gene that is able to do a specific function.  In this case the module represents a collective.  Some examples of modules can be segments, cell linages, genetic pathways or signaling pathways.  One such signaling pathway is the Wnt pathway (Wnt is an abbreviation of the integration1 Int1 gen in mice and the homolog wingless Wg gene in Drosophila, W-nt). 

Wnt genes were first detected in mice with breast cancer (integration1) and later the homolog gene (wingless) in abnormal Drosophila embryos.  The knowledge about Wnt genes were found in different model organisms like Drosophila, C. elegans, and Xenopus.  The Wnt proteins are highly conserved and found from Hydra to Humans.  They are secreting signaling molecules that regulate cell to cell interaction during embryogenesis.  These Wnt signals bind to membrane receptors of the Frizzled family, which induce then a signaling cascade within the cell that leads to activation and expression of different target genes.  The Wnt pathway can act through three different signaling pathways, the Wnt-Catenin beta pathway, the Wnt-Calcium pathway and the Wnt-planar cell polarity pathway.  The first one is highly conserved during evolution and is involved in transformation.  The second pathway regulates cell cytoskeletal organization, whereas the function of the third pathway is not well known.  In addition, a dysfunction of the Wnt pathway can also lead to neurodegenerative disorders like Alzheimer’s disease and heard failure.  In the Xenopus frog the Wnt signals induces body axis specification.  In all vertebrates the dorsal and ventral patterning of the neural tube development is achieved by different gradients of Wnt and Sonic Hedgehog (Shh).  In this case Wnt is found mostly in the upper part of the neural tube, whereas Shh is found on the floor of the developing tube.  These gradients cause the ventral specification and dorsal specification.  On the other hand if Wnt genes or genes

A model for how Wnt signaling influences the specification of cell fate in the mouse ventral neural tube. At E8.5, Wnt signaling is active throughout the neural tube when Shh signaling is initiating in the floor plate. As development proceeds, there is a shift of Wnt signaling in the ventral spinal cord. From ventral to dorsal, progenitor cells are released from Wnt signaling gradually. The release from Wnt signaling creates a permissive environment for cell fates to be specified. Wnt signaling promotes dorsal cell fates through the activation of dorsal genes (in particular Msx1/2) and of Gli3, which encodes a major repressor of Shh signaling. Shh signaling, in turn, may induce Wnt inhibitors, such as sFRPs (secreted frizzled-related proteins), to antagonize Wnt signaling. Hh, Hedgehog.    

             

within the pathway are mutated, developmental processes will be affected.  In humans for example, a malfunction in the Wnt genes or pathways can cause cancer.  The Wnt pathway is a very important pathway because it is conserved through different species, and of course is also important in the evolutionary developmental biology.

The Wnt/β-catenin signaling pathway/ The Wnt pathway in a normal and in a tumor cell

References:

1. Citing webpage, Biomedical Tissue Research Group http://www.york.ac.uk/res/btr/imagelibrary.html. Retrieved on April 13, 2013
2. Citing webpage, Wnt signaling determines ventral spinal cord cell fates in a time-dependent manner. http://dev.biologists.org/ Retrieved on April 13, 2013.



16) Developmental Constraints and Morphological Evolution (by: Rey J. Rosa Morales)

        Traditional neo-Darwinian theory explains how natural selection, genetic drift, and gene flow, acting on the raw material of genetic variation, have produced the astonishing variety of organisms. But does it explain why organisms have not evolved certain features, or in certain directions? Does it explain why there are no live-bearing turtles, for instance, or why frogs have no more than four digits on their forelimbs? Such questions have led evolutionary biologists to ask what the constraints on evolution might be.

        Several kinds of constraints on evolution have been distinguished. Some are universal, in that they affect all organisms; an example is the constant presence of gravity during morphogenesis. Others, referred to as Phylogenetic Constraints, are more local, affecting only a group of related organisms. There are several types of constraints on evolution:

1. Physical constraints. Some structures do not evolve because the properties of biological materials (e.g., bones, epidermis, DNA, RNA, etc.) do not permit them.
2. Selective (or functional) constraints. Some features do not appear in particular lineages because they are always disadvantageous, or because they might interfere with the function of an existing trait.
3. Genetic constraints. Genetic variation in a particular phenotype may not be present. Developmental pathways are expected to have varying degrees of tolerance for variation in their components, and their limits of tolerance may limit variation in the resulting traits. Genetic constraints, such as paucity of variation and genetic correlation, are closely related to developmental constraints. 
4. Developmental constraints. Maynard Smith et at. (1985) defined a developmental constraint as "a bias on the production of various phenotypes caused by the structure, character, composition, or dynamics of the developmental system."  The two most common phenomena attributed to developmental constraints are absence or paucity of variation, including the absence of morphogenetic capacity (i.e., lack of cells, proteins, or genes required for the development of a structure), and strong correlations among characters, which may result from interaction between tissues during development or the involvement of the same genes or developmental pathways in multiple morphogenetic processes.

     Developmental constraints can be revealed by embryological and genetic manipulations in the laboratory. For example, in a classic experiment, Pere Alberch and Emily Gale (1985) used the mitosis-inhibiting chemical colchicine to inhibit digit development in the limb buds of salamanders and frogs (Figure 1 below). The treatment consistently caused specific digits to be missing in each species, and the missing digits were the preaxial ones in frogs and the postaxial ones in salamanders. These results reflected the different order of digit differentiation in the two species; the last digits to form tended to be the most sensitive to the colchicine treatment. Furthermore, the results strongly reflected evolutionary trends: salamanders have often lost postaxial digits, and frogs have repeatedly experienced preaxial digit reduction, during evolution. Although the digit number variation in the study bias produced artificially, the results suggest that naturally occurring variation in developmental systems may be constrained by intrinsic, species-specific developmental programs.

Figure 1. Evidence for developmental constraints.  (A) X-ray of the right hind foot of an axolotl salamander (Ambystoma mexicanun), showing the normal five-toed condition. (B) The left hind foot of the same individual, treated with an inhibitor of mitosis during the limb bud stage. The foot lacks the postaxial toe and some toe segments, and is smaller than the control foot. C) A normal left hind foot of the four-toed salamander (Hemidactylium scutatum) has the same features as the treated foot of the axolotl in B. (From Alberch and Gale 1985; photos courtesy of the late P. Alberch.)

References:

1. Alberch, P., S. J. Gould, G. F. Oster, and D. B. Wake. 1979. Size and shape in ontogeny and phylogeny. Paleobiology 5: 296-317.
2. Futuyma, D.J. (2005). Evolution. Sinauer Associates, Inc. Publishers Sunderland, Massachusetts U.S.A.
3. Palmer, RA (2004). "Symmetry breaking and the evolution of development". Science 306 (5697): 828–833.

17) Bringing Dinosaurs back to life with evo devo from Jack Horner and Hans Larsson (by Theodor Zbinden)

Jack Horner is a paleontology professor at the Montana State University and also a curator of paleontology at the Museum of the Rockies in Bozeman, Montana.  Horner is one of the best known American paleontologists and one of his most prominent discoveries is the fact that Dinosaur cared for their young.  He named various new dinosaur species and two are named after him; Achelousaurus horneri and Anasazisaurus horneri.  He also was the technical advisor for all of the Jurassic Park films.  In 2009 Horner published a book named How to Build a Dinosaur: Extinction Doesn’t Have to be forever.  With the help of Evo devo, Horner planes to revive dinosaur from chicken embryos.  An additional discovery of Horner is that chicken have evolved from dinosaur.  He would like to turn the evolutionary clock backward, but this can be done just because today exist the knowledge of the evolution of the fossil record and the developmental pattern of modern animals.  Evo devo is the only scientific field that connects evolution with development.  Horner thinks that the genes used in the dinosaur are still present in the chicken but they are not active, now the key is how to activate or regulate them again.  He thinks that it is not necessary a whole new suite of genes, it is just needed to adjust the existing genes in activating some and deactivating others.  Chicken and Dinosaur have a very similar skeleton, the difference between them should be eliminated just by adjustments of gene acting in the basic body plane.  If we take, as an example the disappearance of the tail, dinosaur had one but chicken don’t.  We can ask ourselves how the tail disappeared or we can ask ourselves what we can do to reappear the tail again.  Or we may ask ourselves, what can we do to recreate at onec the whole dinosaur from a chicken embryo.  Currently there are birds species that have a tail like structure, and the surprising thing is that in the early developmental stages of the chicken embryo a tail is starting to growth.  But some molecular signals cause to stop that growing.  If it is possible to find out what factors are implying the stopping of the tail growth, it should be possible to inhibit these factors to led growth the tail.  The tail example is just one aspect of growing a dinosaur out of a chicken.  But it shows how it could be done for the entire animal.  For other organs like the teeth’s the knowledge already exists of how they grow in other species .  The idea of growing a dinosaur from a chicken embryo would be to inject different growth factors into a chicken embryo at different stages during the development.  The researcher would play the role of a conductor of an orchestra, activating and deactivating genes producing a dinosaur with activating and deactivating dormant chicken genes with the help of the evo devo knowledge.  So, maybe in the near future Horner and his will be able to create a chicken-dinosaur like animal with the help of the evo devo scientific knowledge.

Jurassic World' Scientist: We Can Bring Dinosaurs Back to Life With...Chickens!

Reference:

1. Citing webpage. Builing a dinosaur from a chicken. Retrieved Aplil 8, 2013. http://www.youtube.com/watch?v=0QVXdEOiCw8
2. Jack Horner, James Gorman.  Jack Horner's plan to bring Dinosaurs back to life. Discovery, the magazin of science, technology, and the future. Issue, April 2009.



18) The study of EDB in humans beings (by Rey J. Rosa Morales)

Figure 1. Human embryo stages.

         
        One of its most important and fascinating endeavors for evolutionary developmental biology will be to elucidate the developmental genetic and evolutionary mechanisms involved in the appearance of traits unique to humans, such as our large brain (figure 2) size, craniofacial morphology, vertebral, limb, and digit innovations, reduced hair cover, and, of course, our complex behavioral and cultural traits (figure 3 and 4). Based on studies in model organisms, we can wait that many of the innovations that evolved in the human lineage involved several or many genes. Comparative genomic data indicate that many or most of the DNA-level changes responsible caused alterations in the regulation of developmental and structural proteins that we share with our primate and mammalian relatives. A conservative estimate of the divergence in single-copy nucleotide sequence between the human and chimpanzee genomes is about 1.2 percent. Given the human genome size of about 3 x 109 base pairs, and assuming that half of this divergence (i.e., 0.6 percent) occurred in the human lineage, about 18 million base pair changes separate humans from the common ancestor we share with chimpanzees. According to Carroll (2003), assuming that the approximately 30,000 human protein-coding genes encode proteins with all average length of 400 amino acids, then only about 1.5 percent (270,000) of the 18 million substitutions will reside in protein-coding regions, and only about 200,000 of these will result in amino acid replacements, the rest being synonymous substitutions. This number could be an overestimate, as there is expected to be relatively less divergence in coding than in noncoding regions.

Figure 2. Human brain

Figure 3. (A) Urbilateria is the archetypal animal that was the last common ancestor shared by protostomes and deuterostomes. (B) The new animal phylogeny, showing that cnidarians are basal to bilateria and that protostomes are divided into two branches, the molting Ecdysozoans and the nonmolting Lophotrochozoans (De Robertis et al., 1990).

Figure 4. The Hox complex has been duplicated twice in mammalian genomes and comprises 39 genes. Note that microRNA genes, which inhibit translation of more anterior Hox mRNAs, have been conserved between Drosophila and humans (De Robertis, 2008).

        It will be an enormous work, much more complex than simply sequencing the human and chimpanzee genomes, to determine which of these amino acid replacements, and which of the many millions of potential regulatory DNA substitutions, have been involved in adaptive evolution of human morphological and behavioral traits. The answers to our questions about specific adaptations will have to come on a trait-by-trait and gene-by-gene basis analysis. This work will be of great interest not only to evolutionary biologists, but also to medical and pharmaceutical researchers. Many of the initial clues to the genetic bases of human traits come from studying human variation, including genetic disorders, and development in mammalian model species, such as the mouse. One critical and long-standing question that "human EDB" should eventually be able to shed light on is whether the genes underlying trait variation within the human species are the same as those involved in divergence from our relatives (Figure 5), the great apes. We can expect that such evolutionary knowledge will can apply concurrently and synergistically with advances in medicine and human developmental biology.

Figure 5. Human evolution 

References:

1. Carroll, S. B. 2003. Genetics and the making of Homo sapiens. Nature 422: 849-857. Chen, F.C., and W.H. Li. (2001). 
2. Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am. J. Hum Genet. 68: 444-456.
3. De Robertis, E. M., G. Oliver and C.V.E. Wright (1990). Homeobox genes and the vertebra body plan. Scientific American 263, 46-52.
4. De Robertis, E. M. (2008). Evo-Devo: Variations on Ancestral Themes. Cell 132, 185-195.