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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 June 9, 2014

 



In the developing nervous system, migrating cells and axons are guided to their targets
by chemotaxis. Members of four protein families — netrins, semaphorins, ephrins and slits
— are involved in this process. Related article: Nature: Netrin-1 and its receptors in tumorigenesis

 






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How brain neurons sense chemical cue to cross-over

Symmetry is inherent in development. An embryo brain and spinal cord, like the rest of its body, organize into left and right halves as they grow. But a certain set of nerve cells do something unusual: they cross from one side of the brain to the other.

New research using mice delves into the details of the molecules guiding these neurons and appears in Science Online.


In an embryo, a neuron’s branches, or axons, have special structures at their tips that sense chemical cues. These cues tell neurons in which direction to grow. Researchers at Memorial Sloan Kettering Cancer Center and The Rockefeller University, identified the structural details of how one such chemical cue — Netrin-1 — interacts with two sensing molecules on the axons. DCC and a previously less well known player — neogenin, are a part of this process.


“Our work provides the first high-resolution view of the molecular complexes that form on the surface of a developing axon telling it to move in one direction or another,” says Dimitar Nikolov, a structural biologist at Memorial Sloan Kettering. “The details of these assemblies help us understand neural wiring, and may one day be useful in the development of drugs to treat spinal cord and brain injuries.”


In a developing nervous system, the signaling molecule, Netrin-1, identified by professor Marc Tessier-Lavigne and colleagues, guides neurons by attracting or repulsing them. In the case of axons that cross from one side of the brain to the other, Netrin-1 attracts them toward the middle.

Using X-rays to visualize the structure of crystalized proteins, research scientist Kai Xu found that Netrin-1 has two separate binding sites on each opposite neural end, enabling it to simultaneously bind to different receptors. This may explain how Netrin-1, an important axon-guiding molecule, can interact with neurons in different combinations.

In experiments that complemented their structural work, the scientists confirmed that just like DCC, neogenin senses Netrin-1 when growing commissural neurons in mice. These neurons are part of the system by which the brain controls movement on the opposite side of the body. Therefore, a mutation in the gene responsible for producing DCC interferes with brain cross coordination, causing congenital mirror movement disorder.

People with this disorder cannot move one side of their body isolated from the other. For example, a right-handed wave is mirrored by a similar gesture using the left hand.

This research has implications for understanding why DCC, neogenin and other cell-surface receptors come in slightly different forms called splice isoforms. These isoforms bind differently to Netrin-1. Nikolov, however, is not yet clear what this means for neuron wiring.


“With this structural knowledge, and with the identification of an additional receptor involved in axon guidance in the spinal cord, we are getting deeper into the mechanisms that produce a functioning nervous system, and the dysfunction that arises from miswiring connections.”

Marc Tessier-Lavigne, professor, Rockefeller University.


Abstract
Netrins are secreted proteins that regulate axon guidance and neuronal migration. DCC is a well-established Netrin-1 receptor mediating attractive responses. We provide evidence that its close relative neogenin is also a functional Netrin-1 receptor that acts with DCC to mediate guidance in vivo. We determined the structures of a functional Netrin-1 region, alone and in complexes with neogenin or DCC. Netrin-1 has a rigid elongated structure containing two receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal two distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains FN4 and FN5, which differs among DCC and neogenin splice variants, providing a basis for diverse signaling outcomes.

Netrin-1_Xu_paper_05302014 Science Online: May 29, 2014
Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism

Kai Xu, Zhuhao Wu, Nicolas Renier, Alexander Antipenko, Dorothea Tzvetkova-Robev, Yan Xu, Maria Minchenko, Vincenzo Nardi-Dei, Kanagalaghatta R. Rajashankar, Juha Himanen, Marc Tessier-Lavigne and Dimitar B. Nikolov

http://newswire.rockefeller.edu/2014/05/30/research-details-how-developing-neurons-sense-a-chemical-cue/

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