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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 Oct 27, 2014

The perichondrium is dense irregular connective tissue that surrounds cartilage in
developing bone. Embryonic stem cells can be stimulated to become chondrocytes
— the cells which will form cartilage and later become bone.
Image from the Office of Educational Technology, School of Medicine, UCSF

 







CDC Growth Standards 0 to 2 Years of Age


 

Recipe to make bone and cartilage

Scientists have combined small molecules from several mouse embryos and made bone and cartilage. This new method is a promising approach for repairing defects in human bone and cartilage.

The research was conducted by The University of Texas Health Science Center at Houston (UTHealth), Monash University and RIKEN Centre for Developmental Biology, and is published in Development.

Using adult stem cells, current strategies regenerate bone and cartilage from these already committed cells — but with limited success. However, the team — led by a holder of the Jerold B. Katz Distinguished Professorship in Stem Cell Research at the UTHealth Medical School, Naoki Nakayama PhD — took a different approach.

Dr. Nakyama chose to work with pluripotent stem cells from early mouse embryos. Pluripotent means that these cells have the potential to become any cell type. To persuade these embryonic stem cells to become cells which will form cartilage (chondrocytes) and subsequently to become bone, the team chose to use small molecules.


"Current cell generation strategies generally use proteins to stimulate stem cells into becomming specialized tissue cells. These proteins affect target cells through multiple mechanisms. But proteins are unstable and expensive to make, and their cost is one of the hurdles limiting scientists in making amounts large enough for what is needed for clinical purposes.

"In contrast, small molecules are generally longer-lasting than proteins in culture — and are inexpensive to produce on a large scale. Small molecules also respond in a more precise manner when differentiating into cartilage and bone. Similar strategies to replace proteins in order to establish better culture methods and maintain pluripotent embryonic stem cells to induce early neural precursor cells have already been used."

Naoki Nakayama PhD, Center for Stem Cell & Regenerative Medicine, UTHealth Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.


Using embryonic stem cells and small molecules, the team was able to generate cells that look and behave like chondrocyte precursor cells that are destined to form cartilage. When that cartilage was transplanted into mice, bone-like structures were later able to form.

This team's strategy offers great hope for the repair of bone defects through cartilage or potentially of damaged cartilage itself in the future, "because it can easily be scaled up to reproducibly produce large numbers of cartilage-forming chondrocyte precursors," said Nakayama.

Abstract
Pluripotent embryonic stem cells (ESCs) generate rostral paraxial mesoderm-like progeny in 5-6 days of differentiation induced by Wnt3a and Noggin (Nog). We report that canonical Wnt signaling introduced either by forced expression of activated β-catenin, or the small-molecule inhibitor of Gsk3, CHIR99021, satisfied the need for Wnt3a signaling, and that the small-molecule inhibitor of BMP type I receptors, LDN193189, was able to replace Nog. Mesodermal progeny generated using such small molecules were chondrogenic in vitro, and expressed trunk paraxial mesoderm markers such as Tcf15 and Meox1, and somite markers such as Uncx, but failed to express sclerotome markers such as Pax1. Induction of the osteochondrogenically committed sclerotome from somite requires sonic hedgehog and Nog. Consistently, Pax1 and Bapx1 expression was induced when the isolated paraxial mesodermal progeny were treated with SAG1 (a hedgehog receptor agonist) and LDN193189, then Sox9 expression was induced, leading to cartilaginous nodules and particles in the presence of BMP, indicative of chondrogenesis via sclerotome specification. By contrast, treatment with TGFβ also supported chondrogenesis and stimulated Sox9 expression, but failed to induce the expression of Pax1 and Bapx1. On ectopic transplantation to immunocompromised mice, the cartilage particles developed under either condition became similarly mineralized and formed pieces of bone with marrow. Thus, the use of small molecules led to the effective generation from ESCs of paraxial mesodermal progeny, and to their further differentiation in vitro through sclerotome specification into growth plate-like chondrocytes, a mechanism resembling in vivo somitic chondrogenesis that is not recapitulated with TGFβ.

Other Authors
Zhao, J., Li, S., Trilok, S., Tanaka, M., Jokubaitis-Jameson, V., Wang, B., Niwa, H. and Nakayama, N. (2014). Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somatic chondrogenesis program from embryonic stem cells. Development, 20, 3848-3858.

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