Animals come in all shapes, sizes and textures. Some have fur, while others have scales. Some lay eggs and others are jelly-like. Ever wonder how all these structures are created or why animals are so different? When zoology museums were first created, they served as a place to preserve animals brought from distant lands, animals no one had ever seen. People were fascinated by the then curiosities, but they were more than curiosities—preserved animals were also used for study. Naturalists were interested in deciphering how all these animals came into being, why they had their unique features and how they all linked together. In order to understand a new species, they would need to compare them to the ones they already knew. This way, they could classify new species and study how they developed.

Scientists would go to great lengths to understand animal biology. Edward Wilson was the scientific advisor for Robert Falco Scott’s final expedition to Antarctica. To study how species evolved, Wilson wanted to collect emperor penguin eggs. Thinking that penguins were primitive birds, he thought he might find a link between reptiles and birds by studying penguin embryos. They managed to collect five eggs but two of them cracked. With great difficulty and under adverse weather conditions, to say the least, they managed to return the three remaining eggs back to camp. Ultimately all but one of the men in the expedition died, but the eggs made their way back to London and the embryos were dissected. The link they were looking for was never found, but their story illustrates the incredible lengths they went to further their understanding of animal biology. This was how scientists studied animals and overall the natural world and its evolution: by collecting, studying and comparing.

Emperor penguin eggs brought back from the 1911 Terra Nova expedition to the Antarctic. The holes were made to allow investigation of the embryos. (Image: © The Trustees of the Natural History Museum, London. Licensed under the Open Government Licence)

Nowadays there are more tools to understand animal biology and evolution. Tissue engineering is the branch of biology that is concerned with studying cells, the materials that support the cells and the chemicals that control the cells. It studies how tissues, like bone or cartilage, are formed. And it aims to build organs, like a liver or a heart. At the same time, tissue engineering goes hand in hand with stem cells, which are immature cells that have the capacity to form any tissue in the body. Thus, organs can be created by growing stem cells together with materials that function as scaffolds.

Tissue-engineered porcine heart (Image: courtesy of Otto Lab for Organ Engineering and Regeneration, Massachusetts General Hospital)

Stem cells and tissue engineering are aiding in the study of evolution and animal biology. At the moment it is very hard to obtain a fully mature and functioning organ, but scientists are growing organoids. These are bulks of stem cells that can grow into similar structures that replicate an organ. In other words, organoids are growths of cells that resemble an organ. Organoids are immature but they are useful to study how organs develop and behave.

Scientists are interested in growing organoids from different animal’s stem cells. This way they can directly compare how they grow and analyse their differences. Imagine growing a lion, a whale and a chimp’s heart organoid side by side in the lab. This is a new way of doing comparative anatomy—organoids. One day, tissue engineering will allow researchers to grow mature functioning organs and, why not, maybe even whole animals in the lab. This way, researchers won’t have to go all the way to Antarctica to collect eggs, they could just grow them closer to home! But until that day comes, organoids provide an invaluable opportunity to study the evolution and development of species by analysing their similarities and differences.

Intestinal organoids (Image: Gianmaria Liccardi, PhD/The Institute of Cancer Research)

Cerebral organoid (Image by Lisa Nguyen, Yaoming Wang and Angeliki Nikolakopoulou, USC Stem Cell)

References:

Hampton T. Organoids Reveal Clues to Gut-Brain Communication. JAMA. 2017;318(9):787–788. doi:10.1001/jama.2017.11545

The Grant Museum has a number of embryological wax models on display (Images 1, 2, 4, and 5 amongst others not shown here). These models, while often ignored by visitors, are actually quite remarkable as they showcase the brilliance and mystery of embryological development. They were created to help elucidate essential questions like: how do humans and other animals form? How are a bunch of seemingly insignificant cells, with no shape other than a ball, able to grow so much and in such detail to form intricate patterns like our eyes? How can one cell transform itself into such different tissues, from hard rock bone to the jelly like liver? In order to understand how a human body is formed it is vital to study the very first stages of its creation, i.e. when we are just a bunch of cells.

Image 1. Placental mammal embryo (Z3100)

The very first cells that are formed after fertilization are called stem cells and they start with an unlimited capacity to form any type of cells. With time, they start to differentiate and mature into specialized cells with a limited lifetime. In this process, little by little they lose their unlimited capacity until they can only form cells that are similar in lineage. In this manner, totipotent stem cells can form any body part including extraembryonic tissue like the placenta. On the next level, pluripotent stem cells (embryonic stem cells for example) are capable of forming any body part but have lost the capacity to form extraembryonic tissue. And finally, multipotent stem cells, much more restricted, can only form cells from a specific tissue or organ.

This may appear as a straightforward process, but the development of an animal is a deeply specific, delicate, and sophisticated interplay of signals and coordinated transitions. Think of it as an orchestrated dance of on and off switches leading to specialisation and exponential growth. In fact, it is so complex that we still don’t understand it entirely.

Although not all human, the wax models display the first stages of development of vertebrates and closely related animals. First, one cell divides symmetrically into two, then four, then eight and so on (Image 1 and front models of Image 2). Afterwards, cells start organizing themselves answering to chemical and physical signals and different patterns start to appear (Image 2 models in the back). Eventually, an axis emerges on which cells migrate along which will give rise to the head on one side and the body and limbs on the other (Image 4). 

Slowly but surely, we all go from looking like little worms to fully grown animals (Image 3). It is important to note that in this initial period most embryos have a very similar appearance, at least between vertebrates. These similarities tell us that a lot of the genes that govern this initial growth haven’t changed between species over time. It’s like nature is saying, “well, if it ain’t broke don’t fix it” and so these mechanisms have been conserved in different animals.

Image 2. Branchiostoma sp, Lancelet Embryo (fish-like invertebrate; T114)

These early stages are crucial moments because if one little element of the spatial/temporal organization is out of place, improper organization can lead to lifelong malformations, diseases, or even the termination of the embryo. Hence the importance of understanding how this process works. We know that even in adult life, there are still stem cells proliferating and forming new tissue to a certain degree. Some organs, like the skin, have a lot of stem cells to replace old cells when they die or get injured. But other organs like the brain, have a very limited capacity to grow new cells—one of the reasons why a brain is much more difficult to fix.

Image 3. Development of the external form of the human face (LDUCZ-Z480) and development of external form of human embryo (LDUCZ-Z430)

Image 4. Vertebrate embryos. Image taken from https://www.ncbi.nlm.nih.gov/books/NBK9974/

So can we get back all the limitless capacity there once was in the developing embryo? Even though the genetic and molecular mechanisms governing all these changes are still somewhat elusive, researchers are using stem cells and powerful genetic tools to answer this question and decipher every single step of how a human is formed in the womb. Moreover, if we can understand the process, then we can recreate and modify it in the lab, and this is exactly what the field of stem cells and regenerative medicine is trying to do. Imagine having the capacity to grow new organs to be used for transplantation or drug testing. How about growing a brand new functioning leg or arm for amputees? Or studying the mechanisms of diseases like Parkinson’s, leukaemia, diabetes, amongst others. The benefits of harnessing the regenerative potential of cells are far-reaching.

Image 5. Development of the external form of the human face (LDUCZ-Z480).

The exciting field of stem cells and regenerative medicine has come a long way, more than a century has passed from the first time the term stem cells was used in 1906 up until the creation of genetically modified human embryos in 2017. The embryological wax models represent initial efforts of identifying how changes give rise to specific structures and ultimately how an animal comes into existence. Furthermore, the future still holds exciting breakthroughs, there is still a lot to understand about human development and the wax models are a fantastic resource to portray the morphogenetic changes we all once went through.

Resources:

Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Comparative Embryology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9974/

http://www.labonline.com.au/content/life-science-clinical-diagnostics-instruments/article/why-do-all-animal-embryos-look-the-same–236915402