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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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The circadian clock regulates metabolism in epidermal stem cells visible in the high NADH/NAD+ ratio, or as increased glycolysis found at night. This high ratio relates to a higher proportion of stem cells in the S phase of cell division. Image Credit: University of California, Irvine




Circadian rhythms regulate skin stem cell function?

The body clock in mice protects cells from oxygen damage during cell division — which may be true in humans as well.

University of California, Irvine (UC Irvine) scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding and all metabolism linked to feeding and fasting are well known, very little is known if the circadian clock also regulates stem cell functions.

The researchers made sensitive and quantitative measurements of the metabolic state of individual cells within living tissue and discovered that the circadian clock regulates one form of metabolism in these stem cells, known as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging suggests that aging is caused by accumulated damage from metabolism-generated oxygen radicals in stem cells.

The study found that the circadian clock within stem cells shifts the timing of cell division to avoid damage to DNA during oxidative phosphorylation.

Past studies in animals have linked aging to disruption of circadian rhythms. Andersen believes that accelerated aging may be caused by unsynchronized cycles of metabolism and cell proliferation in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to disruption of circadian rhythm as being very common in modern society. One consequence of such disruption could be abnormal function of stem cells and accelerated aging," Andersen added.

•We used a noninvasive method to study epidermal stem cell metabolism in vivo
•The circadian clock regulates intermediary metabolism in epidermal stem cells
•A high NADH/NAD+ ratio, reflecting increased glycolysis, is found during the night
•This high NADH/NAD+ ratio correlates with a higher proportion of stem cells in S phase

Through the use of bulk measurements in metabolic organs, the circadian clock was shown to play roles in organismal energy homeostasis. However, the relationship between metabolic and circadian oscillations has not been studied in vivo at a single-cell level. Also, it is unknown whether the circadian clock controls metabolism in stem cells. We used a sensitive, noninvasive method to detect metabolic oscillations and circadian phase within epidermal stem cells in live mice at the single-cell level. We observe a higher NADH/NAD+ ratio, reflecting an increased glycolysis/oxidative phosphorylation ratio during the night compared to the day. Furthermore, we demonstrate that single-cell metabolic heterogeneity within the basal cell layer correlates with the circadian clock and that diurnal fluctuations in NADH/NAD+ ratio are Bmal1 dependent. Our data show that, in proliferating stem cells, the circadian clock coordinates activities of oxidative phosphorylation and glycolysis with DNA synthesis, perhaps as a protective mechanism against genotoxicity.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

Authors: Chiara Stringari, Hong Wang, Mikhail Geyfman and Viera Crosignani with UCI; and Vivek Kumar and Joseph S. Takahashi.

University of Texas Southwestern Medical Center in Dallas contributed to the study, which received support from the National Institutes of Health (grants R01 AR056439, P50 GM076516 and P41 GM103540).

DOI: http://dx.doi.org/10.1016/j.celrep.2014.12.007

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