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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Sep 25, 2013

 




Villi are fingerlike structures on the inside wall of the gut, crucial to the uptake
of food nutrients by effectively increasing the gut's area of absorption.

Image courtesy of L. Mahadevan and Science/AAAS

Patterns within the gut progress through several characteristic stages during embryonic development.

Images courtesy of L. Mahadevan and Science/AAAS.

Related site on gut development: Gut coils with help from its elastic neighbor


Left to right, the digestive tracts of chick, quail, zebra finch, and mouse embryos, shown with the mesenteric tissue still attached. The top row shows the relative size of the eggs (or embryo, in the case of the mammal).

Composite photo courtesy of N. Kurpios.




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How the gut got its villi

Comparing species, researchers at Harvard SEAS and Harvard Medical School investigate a process they dub “villification” — the body making loops of villi to increase gut surface area.

by Manny Morone 2014

“You are not just a ball of cells,” says Clifford Tabin, George Jacob and Jacqueline Hazel Leder Professor of Genetics at Harvard Medical School (HMS).

The way cells organize within the human body allows us all to function the way we do, but a couple of Harvard professors are concerned as much with that developmental process as with the end result. Tabin shares a common perspective with L. Mahadevan, the Lola England de Valpine Professor of Applied Mathematics at the Harvard School of Engineering and Applied Sciences (SEAS), professor of organismic and evolutionary biology, and professor of physics.

“When I teach medical students, they’re more interested in the rare people who are born with birth defects,” says Tabin. “They want to understand embryology so they understand how things go awry, but I’m more interested in the fact that for everyone sitting in my classroom—all 200 of those medical students and dental students—it went right! And every one of them has a heart on the left side and every one of them has two kidneys, and how the heck do you do that?”

By taking steps back through embryos’ development, researchers in Mahadevan’s and Tabin’s laboratories investigated how the guts of several different animals end up as they do. Their findings, published in a recent issue of Science, reveal that the principles guiding the growth of intestinal structures called villi are surprisingly similar across chickens, frogs, mice, and snakes.

These fingerlike villi lie on the inside wall of the gut and are crucial in the uptake of nutrients from food by effectively increasing the absorptive surface area 30-fold.

Researchers in Tabin’s lab had noticed a zigzag pattern on the inside of the guts of chick embryos, while collaborating on a project that investigated the coiling of the gut.

“They showed me the picture and I said, ‘I know how to explain that,’” recalls Mahadevan, who had studied the cause of such zigzag patterns in shrinking gels in 2005.

Mahadevan’s group uses theoretical and experimental approaches to study a variety of problems in science and engineering. His team's recent interest is the physical basis of morphogenesis in plants and animals. Tabin’s team, on the other hand, has a longstanding interest and expertise in the development of living organisms. Together, the two groups designed and carried out experiments and simulations to elucidate exactly what makes the villi turn out the way they do, a process they dubbed "villification."

Previous studies into villi development only looked at the later stages of villi growth, which is driven by stem cells at the base of their structures. But by pooling their expertise, the two labs confirmed that early villi growth is not driven by the division of stem cells, but by mechanical forces from different muscle layers of the gut.

“It’s as if I had a piece of paper and wet it on one side: the wet region would swell, the dry one would not,” says Mahadevan. “This causes the paper to wrinkle. Similarly, when one layer of the gut grows slower than the other, it becomes compressed and buckles.”


Researchers observed that the wrinkling of the inner gut is intimately linked to stages in muscle layer differentiation.

By looking across animal models, the labs were even able to specify which muscle layers cause which folding patterns. Some animals, like frogs, keep their zigzag guts until birth because they lack a corresponding muscle layer found in chicks and mice, which allows individual villi to form.

Co-lead authors Amy Shyer, a graduate student in Tabin’s lab, and Tuomas Tallinen, a postdoctoral fellow in Mahadevan’s lab, observed that muscle layer differentiation coincided exactly with shifts in patterns observed in the gut.

The scientists constructed computational models of the process of incorporation the gut’s experimentally measured geometry and mechanical properties.


“Now there is a gap,” says Tabin. The group's next aim is to explain interim growth, after the individual villi have been formed but before they are entirely dependent on stem cells for their preservation. More knowledge on this force-to-stem-cell transition will lead to a broader understanding of other developmental mechanisms that cannot be observed in organisms after birth.

The implications of this work lie in the power of the physical approach to be generalized for organs in other species.

“There’s a very simple principle explaining these patterns: how leaves curl, how tendrils form, how the gut forms," says Mahadevan. "They all arise because of differential growth, which leads to shape changes due to geometric incompatibility."

“The people coming from the developmental biology world—the non-mathematical world—were not thinking in terms of physical forces,” says Tabin. “Then there was a second world of those who think mechanically, who think about how tubes fold in a biological setting.”

Alone, each perspective cannot, for example, fully paint the picture of villus formation, but studies like this help to build bridges across traditional disciplines.

Abstract
The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and finally individual villi. We find that these steps of villification depend on the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. A quantitative computational model, incorporating measured properties of the developing gut, recapitulates the morphological patterns seen during villification in a variety of species. These results provide a mechanistic understanding of the formation of these elaborations of the lining of the gut, essential for providing sufficient surface area for nutrient absorption.

The research was supported by the National Institutes of Health (R01 HD047360), a MacArthur Foundation “genius” grant to L. Mahadevan, and a grant from the Finnish National Science Foundation. In addition to his roles at Harvard SEAS and in the departments of physics and organismal and evolutionary biology, Mahadevan is a core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard and a member of the Kavli Institute for Bionano Science at Technology, which is based at SEAS.

Coauthors included Nandan L. Nerurkar, a research fellow in genetics at HMS; Zhiyan Wei, a graduate student at SEAS; and Eun Seok Gil and David L. Kaplan of Tufts University.

Original press releas: http://www.seas.harvard.edu/news/2013/09/how-gut-got-its-villi