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Archive for the 'Citlali Helenes Gonzalez' Category

Why are animals 3D?

By Citlali Helenes Gonzalez, on 23 November 2017

 

Have you heard that our body is mainly composed of 70% water? Although true, the percentage varies from 55% of water in adult women, all the way up to 78% in babies, with the percentage for adult men somewhere in between. This is also true for animals, where some — like the jellyfish — have even 90% of their body composed of water. With this in mind, why don’t animals, including us, look like a soup? How can animals have a defined 3D structure?

Aurelia aurita, moon jellyfish, 5 preserved specimens (C193)

Aurelia aurita, moon jellyfish, 5 preserved specimens (C193)

 

Animals are made out of cells, the building blocks of our organs and tissues. But cells are basically a bag of water and chemicals; so again, why don’t animals look like giant bags of chemicals? The most obvious reason is that animals have bones that give structure to the rest of the body. But even bones are 31% water, and organs with no bones, such as hearts, still have a unique 3D form. Hearts have defined chambers (see the elephant heart below); they’re not just a mush of cells. The answer lies not in the cells themselves but in what surrounds them.

Elephant dried heart (Z639)

Elephant dried heart (Z639)

Cells are engulfed by the extracellular matrix (ECM) which is mainly composed of proteins. This matrix encompasses the space in-between cells, gives them structural support and acts like a scaffold. It can also act as a pathway for cells to migrate along and it gives out chemical and physical cues that cells respond to. The ECM varies from organ to organ. The brain, for example, is mainly composed of cells with an ECM of only 20% of the total mass. In contrast, cartilage has fewer cells and around 70% of its mass is ECM. Every cell type is surrounded by a specific matrix that will affect its function. Studying this extracellular environment is important to understand how cells develop, how they interact with each other, and how they react to disease.

At the same time, by studying the ECM, researchers can get an idea of how an organ or tissue is structured and how to replicate its intricate architecture. Scientists that work in tissue engineering use a technique which consists of washing away the cells of an organ, literally. By using detergents, the cells are washed away in cycles until just the extracellular matrix is left. In this manner, they can analyse its composition and experiment with the matrix with the end goal of growing an organ in the lab. Therefore, one day we could replace diseased or aged organs with new ones without the need for transplantation. The unique composition of the ECM provides cells with the support they need to survive, and at the same time, gives animals and their organs a defined 3D structure.

 

Sources:

https://water.usgs.gov/edu/propertyyou.html

How to visualize the insides of an animal?

By Citlali Helenes Gonzalez, on 26 October 2017

When studying animals, sometimes we need to study them from the inside out —literally. One way to do this is to cut them open and looking at their internal structures, such as with the bisected heads or the microscope slides in the Grant Museum of Zoology. Another way to visualize the inside of an animal is to stain a particular body part while making everything else clear; researchers can do this by using chemicals and colour stains. For example, in the Grant Museum of Zoology, we can find specimens like the tarsier, with its skeleton stained in red, or the zebrafish with red and blue parts.

Adult tarsier stained with Alizarin Red to show calcium (Z2718)

Adult tarsier stained with Alizarin Red to show calcium (Z2718)

Adult zebrafish stained with Alcian Blue and Alizarin Red (V1550)

Adult zebrafish stained with Alcian Blue and Alizarin Red (V1550)

 

The process of staining these animals begins with the removal of the skin, viscera and fat tissue.  Then, soft tissues like muscle are cleared using a variety of different methods which mostly involve exposing the specimen to different baths of chemicals. Next, the bones are stained with Alizarin Red and the cartilage with Alcian Blue. It’s a long process that can take a couple of days because the stain needs to properly penetrate the tissues, but the results are amazing.

Initially, both Alizarin Red and Alcian Blue were used as textile dyes, but now they also have numerous biological applications. Alizarin Red staining is a method to visualize mineralized tissue because it stains calcium and Alcian Blue stains specific structures mainly found in cartilage. These stains constitute an important part of research because they allow researchers to visualize the intricate structure of tissues and thus understand how they form throughout development.

ADSCs

Image credit: Eleonora Zucchelli

In the lab where I study, researchers work with adipose (fat) derived stem cells which have the capacity to become different kinds of mature cells. These stem cells are grown under specific conditions and by changing these conditions scientists can direct them into becoming mature cells like fat, bone or cartilage — a process called differentiation. But this process can take anywhere from a couple of weeks up to a couple of months! In order to determine if the differentiation is working, researchers stain the stem cells with Alizarin Red and Alcian Blue to identify if they are in fact turning into bone or cartilage. In the images depicted, undifferentiated adipose derived stem cells (ADSCs) on the top appear clear but their differentiated counterparts are stained in blue or red. This means the differentiation is working.

There are many other stains used on animals or cells. The process of clearing and staining can be very complicated depending on the specimen and what one wishes to stain, but the results can be quite fascinating. What animal would you like to see stained from the inside.

 

Mouse stained with alizarin red (Z3155)

Mouse stained with alizarin red (Z3155)

 

References:

PUCHTLER, H., Meloan, S. N., & TERRY, M. S. (1969). On the history and mechanism of alizarin and alizarin red S stains for calcium. Journal of Histochemistry & Cytochemistry17(2), 110-124.

McLeod, M. J. (1980). Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology22(3), 299-301.

 

Embryological Wax Models

By Citlali Helenes Gonzalez, on 14 September 2017

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)

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)

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 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/

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).

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

Are whales and dolphins as smart as we are?

By Citlali Helenes Gonzalez, on 10 August 2017

Although humans are land mammals, we still occupy marine environments whether for work, leisure or exploration. But real sea mammals have adapted to living their entire lives in the ocean and the best adapted are whales and dolphins. Over time their adaptations have allowed them to live in a world with hardly any shelter where sound is more important than sight. Being smart and able to cooperate plays a vital role in surviving in this kind of environment.

One thing we have in common with whales and dolphins is that we have big brains. How big? Without taking into account body size, sperm whales have the biggest brain in the world weighing around 7.8 kg. But in proportion to body size, humans have a bigger brain followed closely by dolphins; strangely enough, whales have a smaller brain than most seals.

Delphinus sp Common dolphin Grant Museum Z2277

Delphinus sp
Common dolphin
Grant Museum Z2277

It would make sense to think that a larger brain has more neurons and therefore more cognitive power; but does brain size correlate with cognitive ability? Not necessarily—brain size does not tell us the whole story. The cortex is a thin layer of cells (2-4 mm) that constitutes the outermost layer of the brain and gives it its characteristic wrinkly appearance. The cortex is where all the higher cognitive functions take place, where our senses are processed and where consciousness, thought and language is formed. Because of this, we might assume that having a bigger cortex is the fundamental key to intelligence.

We know that dolphins and killer whales have a much wrinklier cortex than humans, meaning it has a bigger surface area. However, does a bigger cortex mean more neurons? Even though we don’t know the exact number of neurons killer whales or dolphins have, researchers have counted the total number of neurons in the neocortex (part of the cortex) of the minke whale. Although it has a similar thickness to the human cortex, it only has 2/3 of the neurons we have. Even at the cellular level, we don’t yet know what these differences mean. Overall a thick cortex does not necessarily mean more neurons and a big brain does not necessarily mean more cognitive power. Taking into account different parameters, it’s hard to tell which animal is smarter.

However, putting aside our brains, it’s what we can do with them that is interesting. Amongst whales, dolphins and humans, we all share behaviours that could be called culture. I say this carefully because the term culture can have different definitions and there is still debate on whether non-human animals can have culture in the way that we do. But let’s forget about humans—other animals have their own animal culture.

A general definition—taken from the book The cultural lives of whales and dolphins by Hal Whitehead and Luke Rendell—is as follows: “Culture is behaviour or information with two primary attributes: it is socially learned and it is shared within a social community”. In other words, culture is basically what you learn from other members of your community and it’s important to note that it’s not determined by your genes.

For instance, dolphins have sophisticated whistles and calls to communicate and some whales, additionally, have songs. They also have very specific ways of feeding depending on where they live and who they “hang out” with. The bottlenose dolphin, for example, has at least 20 different types of hunting. This does not mean that every bottlenose dolphin around the world knows 20 different types of hunting. This means, that depending on their social group and environment, they develop different skills. So one group of dolphins in the Caribbean might hunt a specific fish in a certain way while others in another part of the world do it differently. Even neighbour dolphins might hunt differently depending on who they form social bonds with. Similarly, whale songs can be in or out of fashion changing rapidly and spreading throughout the whole population of whales (grey whales in this case). All of these behaviours could be called culture because they are socially learned and are not determined by genes.

Moreover, why is culture so important? Genetic information is passed from one individual to another from one generation to the next. Communication of cultural information happens quicker than the flow of genetic information. Culture allows a population to learn something very quickly, and this, in turn, translates into better adaptations to new threats or new environments. Culture is what allows us, humans, to learn much more than what we could possibly deduce for ourselves.

Similar to humans, some would argue that whales and dolphins have culture because they have the ability to communicate information with individuals of their own community. Even if whale/dolphin intelligence or culture does not correlate entirely with our definitions of such, the whole idea of trying to fit them into a human definition is somewhat absurd. Animals adapt to their environment and so, will develop strategies to overcome the hurdles their unique habitat presents; thus if a whale cannot invent the wheel maybe it’s because it doesn’t need to.

In addition to big brains and cortices, humans share more with sea mammals than you might think.   So next time you see a brain or a skull in the Grant Museum of Zoology or any other museum, think about how that brain has evolved to adapt to its particular environment.

whale


Hyperoodon ampullatus Northern bottlenose whale Female Z1112

Sources:

Whitehead, H., & Rendell, L. (2014). The cultural lives of whales and dolphins. University of Chicago Press.

https://blogs.scientificamerican.com/news-blog/are-whales-smarter-than-we-are/

Question of the Week: Why do brains have wrinkles?

By Citlali Helenes Gonzalez, on 27 April 2017

The brains displayed at the entrance of the Grant Museum are mostly mammal’s brains but we can observe differences in sizes and in how smooth or wrinkly they are. The folds of a brain are called gyri and the grooves are called sulci. These morphological features are produced by the folding of the cortex, the part of our brain responsible for higher cognitive processes like memories, language and consciousness. During development, all brains start off with a smooth surface and as they grow, gyrification (the development of the gyri and sulci) occurs. It is interesting to note that the major folds are very consistent amongst individuals, meaning that development is similar sometimes even amongst species.

c_ucl_gmz_matt_clayton020

The brain collection on display at the Grant Museum of Zoology (Image credit Grant Museum of Zoology).

 

It has been assumed that the wrinkles in brains correlate with an animal’s intelligence. The reasoning behind this is that a bigger brain, and hence more neurons, need more space. The folds allow the cortex to increase its area while being packed in a confined space like our cranium. There are several factors and hypothesis of how gyrification occurs. Recently, researchers at Harvard developed a 3D gel model based on MRI (magnetic resonance imaging) images to understand how this process occurs. They found out that it all boils down to the mechanical properties of the cortex. While neuronal cells grow and divide, the increasingly bigger brain leads to a compression of the cortex and to the formation of the folds. The researchers were able to mimic the folds of the cortex and were stunned at how similar their gel model looked to a real human brain.

tumblr_o21mv85Nt01t5fphqo1_1280

Gel model of a foetal brain (Image credit: Mahadevan Lab/Harvard SEAS).

 

Even though most of the brains on display in the Grant museum have gyri and sulci, in nature, most animals have smooth brains. In general, larger brains have folds while smaller brains do not, even small mammals like rats or mice have smooth brains. In humans, a lissencephalic brain is one without gyri and sulci and is a result of a rare disorder that is characterised by mental abnormalities. From the collection of brains in the Grant Museum, there is only one lissencephalic brain—next time you visit the museum see if you can spot it. Additionally, try to find the brain coral. Because of its intricate maze–like pattern, Diploria labyrinthiformis has very similar ridges and grooves as a brain, and so is referred to as brain coral. Overall, I find looking at brains and their grooves fascinating, each species with their own pattern and each groove in a specific place. Makes me wonder how brain coral gets its patterns.

brain coral 3

Diploria labyrinthiformis also known as brain coral(Grant Museum C1084).

 

References:

Roth, G. and Dicke, U., 2005. Evolution of the brain and intelligence. Trends in cognitive sciences9(5), pp.250-257.

Ronan, L. and Fletcher, P.C., 2015. From genes to folds: a review of cortical gyrification theory. Brain Structure and Function220(5), pp.2475-2483.

Manger, P.R., Prowse, M., Haagensen, M. and Hemingway, J., 2012. Quantitative analysis of neocortical gyrencephaly in African elephants (Loxodonta africana) and six species of cetaceans: comparison with other mammals. Journal of Comparative Neurology520(11), pp.2430-2439.

 

Question of the Week:

What is an axolotl and why is it so unique?

By Citlali Helenes Gonzalez, on 4 May 2016

By Citlali Helenes Gonzalez

From the many specimens that are on exhibit at the Grant Museum of Zoology, it is hard to choose one that stands out. For me, it has to be the axolotl, a small little creature that passes by unnoticeable. It is not the biggest or the strangest but it has a unique feature that we humans desire to achieve: tissue regeneration. Although newts, salamanders and starfish can also regenerate tissue, the axolotl is probably the most interesting of these animals because of the extent of its capacity.

20160210_134444When we humans have an injury, our body starts forming scar tissue over the injury. With just a few exceptions, like the skin that is regenerating constantly and the liver that does something similar to regeneration, the rest of our body has very limited regeneration capacity.

The axolotl, on the other hand, after an injury, the tissue at the wounding site starts to regrow new healthy tissue instead of scar tissue. It does so to the extent that it can regrow a whole limb, jaw, tail, spinal cord and even some parts of its brain. Scientists have even transplanted organs from one axolotl to another with no rejection issues. And if all of this is not enough for you to be amazed, the axolotl is over 1000 times more resistant to cancer than mammals. This is why it has been used as a model animal for the study of regeneration and development.

Studying the axolotl has huge implications for medical research because if we can learn how the mechanisms of regeneration in this little animal work, then maybe we can simulate it in humans. And in the long run, if we learn how to regenerate and repair tissue, this could mean no more need for transplants, no more prosthesis of arms or legs, helping burn victims just to name a few benefits.

Unfortunately, this little animal native to Mexico has been listed as an endangered species due to the destruction of its natural habitat in the lakes and canals of Mexico City. But scientists across the globe are still studying them and looking closer into their genome to try to unlock the secrets of tissue regeneration. So next time you stop by the Grant Museum take a closer look at this fascinating animal that even though its small size has a lot to offer to human medical research.

 

Further reading:

Roy, S. and Lévesque, M., 2006. Limb regeneration in axolotl: is it superhealing? The Scientific World Journal6, pp.12-25.

http://blogs.scientificamerican.com/guest-blog/regeneration-the-axolotl-story/

 

 

Question of the Week:

Can we build a brain in the lab?

By Citlali Helenes Gonzalez, on 28 January 2015

 

Citlali Helenes Gonzalez-labWhile working at the Grant museum of Zoology the other day, I encountered a lovely group of teenagers that started asking me questions about the museum. As we engagers do, I automatically started talking about my PhD project. I told them that I was working with stems cells and trying to build a neural tissue in the lab, to which they replied with a tilt of the head in sign of confusion. So I inevitably had to change my explanation and told them that I was trying to build a tiny part of a brain in the lab.

With a change of head tilting they replied with “Uh, that sounds cool” and “Are you going to create a Frankenstein?” To which I, being the bubble buster that I am, had to reply with, “Well, actually, Frankenstein was the scientist that created the monster”. So no, I am not going to create a scientist, or a monster, or a brain. I could see a tiny deception in their faces, so explained that neural tissue doesn’t necessarily mean that I’m building an entire brain, although it would be helpful to have two brains instead of one, especially when writing a thesis!!! But no, scientists have not been able to grow a full size brain. The closest that scientists have come, has been to grow a group of brain cells that self-assembled into an “organoid” that resembles some structures of a brain.

So how is that different from a brain? Good question, I am glad you asked avid reader. Even though the cells scientists have grown have developed into different kinds of brain cells and had some neural activity, the maturation and differentiation of different brain areas was not complete. The connections and systems that make us see or hear or control our movements were not there.

It is not enough to have brain cells arranged together; the information that runs through neurons has to have specific highways and an overall order in the soup of chemicals and cells that is our brain. Besides all the intricate and delicate organization cells need to have, they also need nutrients and oxygen or in other words, blood vessels, little tiny ones and big chunky ones, to reach every cell so that they can survive and function. Yes, there are interesting advances into knowing how the brain works and how cells develop into a brain, but we are not there yet.

So the answer to “Can we build a brain in the lab?” is no, not right now. So contrary to what may have been on the news, lets just say that we can grow brain cells and keep them alive; we can make them interact with each other and grow groups that self-assemble, but we are years away from actually growing a fully functional brain. And in order to have a ”functioning” brain it would need to have eyes and ears and muscles and all of the systems that connect to it (basically a body) in order to be functional. Otherwise it would not have any input and would not be able to process information.

Many of the guys that I was talking to in the museum where relieved when I explained this to them, fearing that maybe science has come too far. Has it? I don’t know, but I will leave you with this question: Do you think it would be a good idea to build a brain in a lab?

 

Infographic from livescience.com:

cerebral-organoid-model-brain-130827a-02