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.