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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
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Home | Pregnancy Timeline | News Alerts |News Archive Aug 14, 2014

Like stripes and dots in many animals, fingers become predictable patterns using the Turing model.


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Turing theory (1952) explains formation of fingers

Research confirms that a mathematical theory, proposed by Alan Turing — designer of the machines that cracked German military codes in 1952 — can explain the formation of fingers.

Alan Turing is the British mathematician (1912-1954) famous for breakthroughs which altered the course of the 20th century. In 1936 he published a paper laying the foundation for computer science, providing the first formal concept of a computer algorithm. He then played a pivotal role in the Second World War, designing machines which cracked the German military codes, enabling the defeat of the Nazis in several crucial battles. In the late 1940's he turned his attention to artificial intelligence and proposed a challenge, now known as the 'Turing Test', which is still used in the field of artificial intelligence.

Turing's contribution to mathematical biology is less famous, but no less profound. He published just one paper (1952), that triggered a whole new field of mathematical enquiry into pattern formation. He discovered that a system with just 2 molecules could in theory, create spotted or striped patterns if they diffused chemically in just the right way.

Alan Turing's mathematical equations showed that two molecules starting from a uniform condition without a pattern, could spontaneously self-organise through chemical diffusion into a repetitive spatial pattern.

This theory has come to be accepted as an explanation of fairly simple patterns such as zebra stripes and even the ridges on sand dunes. But in embryology, it has been resisted for decades as an explanation of how structures such as fingers are formed.

Now a group of researchers from Barcelona, Spain, led by Institucio Catalana de I Estudis Avancats (ICREA) Research Professor James Sharpe, has provided the data confirming that fingers and toes are patterned by the Turing model.

"It complements their recent paper Science which provided evidence that Hox genes and FGF signaling affect a hypothetical Turing system. However, when Turing developed his theory — these molecules were unknown. Turing's theory remained unsolved  waiting for this critical piece of the puzzle. The new study completes the picture, by revealing which signaling molecules complement the Turing system"
explains Dr. Sharpe, co-author of the study.

A systems biology approach was taken to unravel the puzzle – combining experiments with computer modelling. Jelena Raspopovic conducted laboratory experiments, while computer simulations were created by Luciano Marconto.

After reviewing hundreds of genes, Raspopovic and Marconto found two signalling pathways — BMP and WNT— when linked to the gene Sox9 form a Turing network.

After more computational predictions inhibiting these 2 pathways – either individually, or in combination, and experiments on small pieces of mouse limb bud tissue in a petri dish, they confirmed the Turing model.

The research was published in the journal Nature: Scientific Reports and highlights that mechanisms of self-organization may be much more important in organ formation than previously thought.

Understanding multicellular organization is essential to regenerative medicine so that we can engineer replacements tissues and organs. However, in the short term this finding explains why polydactyly – the development of extra fingers or toes – is a common birth defect in humans. Turing's model is known for its imprecision in producing a set number of "stripes".

At first glance, the question of how an embryo develops seems unrelated to computing and algorithms with which Turing is commonly associated.

In reality, both are expressions of his interest in how complex and clever biological "machines" arise in nature. In a sense, Turing looked for the algorithms by which all life builds itself.

It is fitting that this study, which has confirmed Turing's 62 year-old theory on embryology, required the development of a serious computer model. It brings together two of his major life achievements into one satisfying result.

Nature Abstract
Interpreting a morphogen gradient into a single stripe of gene-expression is a fundamental unit of patterning in early embryogenesis. From both experimental data and computational studies the feed-forward motifs stand out as minimal networks capable of this patterning function. Positive feedback within gene networks has been hypothesised to enhance the sharpness and precision of gene-expression borders, however a systematic analysis has not yet been reported. Here we set out to assess this hypothesis, and find an unexpected result. The addition of positive-feedback can have different effects on two different designs of feed-forward motif– it increases the parametric robustness of one design, while being neutral or detrimental to the other. These results shed light on the abundance of the former motif and especially of mutual-inhibition positive feedback in developmental networks.

Article J. Raspopovic; L. Marcon; L. Russo; J. Sharpe. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients. Science, 2014. DOI: 10.1126/science.1252960

Science Abstract
During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation.

Research for the Nature article was conducted in Barcelona, Spain in the Multicellular Systems Biology lab at the Center for Genomic Regulation (CRG), led by Institucio Catalana de I Estudis Avancats (ICREA) Research.

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