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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 Aug 21, 2014

a, Two (pale green) of five VHH15 molecules viewed parallel to the neuron membrane.
b, Perpendicular to the membrane. c, A single subunit of the 5-HT3

 




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Finding the 3-D structure of a neuroreceptor

Neurons are brain cells, working with our spinal cord, and nervous system to form a complex communication network. Chemicals carry the electric signals connecting these systems. These molecular chemicals bind to the surface of neurons via neuroreceptors, opening and closing paths that allow signals to transmit from neuron to neuron. But how does binding occur?

One neuroreceptor, called 5HT3-R, is involved in a range of conditions like chemotherapy-induced nausea, anxiety, and disorders such as schizophrenia. 5HT3-R is so complex, scientists haven't been able to figure out its structure. Published in Nature, Ecole Polytechnique Federale de Switzerland (EPFL) researchers have uncovered the 3D structure of 5HT3-R, opening a way to understanding how it attaches.


The mystery is how the neurotransmitter molecule binds to the membrane of a neuroreceptor to conduct a charge.


Using X-ray crystallography, Horst Vogel's team at EPFL has determined the 3D structure of 5HT3-R, a type-3 serotonin receptor. 5HT3-R recognizes the neurotransmitter serotonin and opens a transmembrane channel that allows electrical signals to pass through. The 5HT3 receptor was first grown in human cell cultures and then isolated before finally being crystallized.

It took years of work before EPFL scientists succeeded in obtaining a a stable complex with 5HT3-R. This complex eventually yielded exceptional quality crystals for X-ray crystallography. Crystals for X-ray crystallography were viewed at the synchrotron facilities in Paul Scherrer Institut, Switzerland, and at synchrotron facilities in Grenoble, Switzerland. A well-established technique, crystals diffract X-rays in shadow patterns from which 3D structures can be reconstructed.


The X-ray diffraction produced a 3D structure for 5HT3-R. The image showed a bullet-shaped 5HT3 receptor with five subunits symmetrically arranged around a central water-filled channel penetrating the neuron's cell membrane.


The cell membrane channel can be in either of two states: closed: electrically non-conducting or, after binding to a neurotransmitter—or—
open: electrically conducting charges to flow in and out of the neuron thus generating an electric signal.


"We have now explained the molecular anatomy of a receptor that plays a central role in neural transmission. It is the first 3D structure of its kind and may serve as a blueprint for the other receptors of this family. In the next step, we have to improve the resolution of the structure, which might give us information on how to design novel medicines that influence this neuroreceptor's function."

Horst Vogel, PhD, Laboratory of Physical Chemistry of Polymers and Membranes, in the Ecole Polytechnique Fédérale de Lausanne, Switzerland


Abstract
Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 Å resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 Å constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.


Authors and Reference
Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A, Moreau C, Li X-D, Poitevin F, Vogel H, Nury H. X-ray structure of the mouse serotonin 5-HT3 receptor. Nature DOI: 10.1038/nature13552


This work represents a collaboration between Ecole Polytechnique Federale de Switzerland (EPFL) Laboratory of Physical Chemistry of Polymers and Membranes; the Center for Cellular Imaging and NanoAnalytics of the University of Basel; the Swiss Light Source and the Laboratory of Biomolecular Research of the Paul Scherrer Institute; the Architecture et Fonction des Macromolécules Biologiques of the Centre National de la Recherche Scientifique; the Université Grenoble Alpes; and the Unité de Dynamique Structurale des Macromolécules of the Institut Pasteur.

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