Spatial and temporal regulation of genes or gene network is essential for proper development of an embryo. Any change in the gene regulation will lead into phenotypic novelty, either due to the change in function of the concerned protein or loss / gain of function in particular tissue. So to understand evolution of development is vital to decipher the origin and evolution of gene regulation and regulatory networks. Mutations affecting gene regulation can be either at the cis –regulatory elements (place where regulatory proteins bind to activate or repress concerned gene-e.g. : enhancer sequences) or in protein itself (coding region).
Studies in the field of evolutionary developmental biology indicate shows that adaptive mutations with phenotypic effects are much more likely to occur in cis-regulatory elements than in protein-coding genes. This accounts for the growing debate in the field of evolutionary and developmental biology concerning the relative contribution of cis-regulatory and protein (particularly transcription factor) changes to developmental evolution. There is significant evidence for the importance of cis-regulatory evolution (For a review on importance of cis -regulatory elements read: Wray GA (2007) The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 8:206–216. ) but not many well worked out examples for the examples of protein-mediated evolution of novel developmental pathways. Many laboratories especially the one of Gunter Wagner in Department of Ecology and Evolutionary Biology, Yale University provide some valuable insights into the changes in transcription factor proteins that undergo adaptive evolution resulting in novel functions and subsequently contributing to the evolution of development.

In one such effort Wagner’s lab looked into the origin and evolution of the placenta and uterus in mammals,which according to them depends on the evolutionary changes in a single regulatory protein.
Pregnancy is an unusual phenomenon seen in all mammals (few exceptions in Bats and Platypus) , where one organism lives and develops inside another that is genetically different.It is considered a key evolutionary innovations of eutherian (placental) mammals and this adaptation was possible by the evolution of uterus and placenta.
Evidence resulting from various genetic and biochemical studies revealed many important genes for pregnancy , which includes many transcription factors, growth factors, and cell signaling molecules. One such signaling molecules is prolactin (PRL), expressed in uterus and its proper regulation is essential for pregnancy. Expression of PRL in this tissue depends primarily on AbdB Hox protein related HOX A11 . Apart from its role in activating PRL ,HoxA11 is also responsible for pre- and postnatal development of the female reproductive tract.
Taking into account the data obtained from evolutionary analysis involving HOXA11 ,which showed an regulatory link in the evolution of pregnancy and altered function HoxA-11.PRL and the prolactin receptor (PRLR) are expressed in the uterus and placenta of placental mammals but not in oviducts of fishes,amphibians and reptiles. Results from Vincent J. Lynch and co authors showed beyond doubt that PRL expression in mammals is a derived feature of placental mammals and this occurred by positive selection in HoxA-11 occurred coincident with the origin of its ability to interact functionally with another transcription factor protein (FOXO1A) and thereby up-regulate PRL in uterus cells. Interestingly HOXA11 from from opossum, the reconstructed therian ancestor, platypus, and chicken failed to up-regulate PRL expression, which goes perfectly with the fact that the positive change they found in HoxA-11 is present in all known placental mammals and not in marsupials, like opossums or wallabies, where there is a brief and rudimentary pregnancy followed by development of the offspring outside the mother, or in egg-laying mammals like the platypus.
With this remarkable work Gunter Wagner’s lab identified for the first time ever some of the initial stages in the evolution of a novel gene regulatory network.This also demonstrates that evolution of development is not only mediated by the evolution of cis-regulatory elements but also requires evolution of transcription factor proteins .

Reference :
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals.
Lynch VJ, Tanzer A, Wang Y, Leung FC, Gellersen B, Emera D, Wagner GP.
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14928-33.

Image Credit:
Matt From London / FlickR

UPDATE :
I found an excellent related article by Todd H. Oakley on origin of placenta in mammals

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