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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.

WHO International Clinical Trials Registry Platform

The World Health Organization (WHO) has created a new Web site to help researchers, doctors and
patients obtain reliable information on high-quality clinical trials. Now you can go to one website and search all registers to identify clinical trial research underway around the world!




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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 Jan 2, 2014


Scientists at Arizona State University, Germany and France have uncovered the key to sex determination in honey bees, one of the most important questions in developmental genetics..

Image Credit: Jacob Sahertian

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Molecular sex switch in honeybees

Only small differences in 5 amino acids separate males from female bees. But it's taken nearly 200 years, for scientists in Arizona and Europe to figure out how this molecular switch for sex gradually evolved in the honeybee.

A Silesian monk named Johann Dzierson proposed the first genetic mechanism for sex determination in the mid-1800s, according to study  lead author and Arizona State University Provost Robert E. Page. Dzierson was trying to understand how males and females were produced in honey bee colonies. He knew the difference between queen and worker bees – both females – emerged from different quality and quantity of food. But, what about the males, he asked.

That male honey bees are haploid – meaning they possess only one set of chromosomes — was confirmed with the advent of the microscope in the 1900s. Under a magnifying lens, scientists could see that eggs that grew into drones were not penetrated by sperm.

How this system of haploid sex evolved at a molecular level has remained one of the most important questions in developmental genetics.

In the December issue of Current Biology, Page and Martin Beye, professor with the Institute of Evolutionary Genetics in the University of Duesseldorf, Germany, and five more scientists, laid out the final pieces of how these systems evolved. Altogether, the researchers studied 14 natural sequence variants of the complementary sex determining switch (csd gene) for 76 genotypes of honey bees.

While complex, the researchers had several tools their predecessors lacked in order to solve this sexual determination puzzle.

First, honey bees are ideal subjects because they have one gene responsible for sex determination. Also, Page and former graduate student Greg Hunt identified gene markers — well-characterized regions of DNA close to the sex determining gene — to begin gene mapping. Hunt and Page also found that the honey bees' high recombination rate — or process by which genetic material is physically mixed during sexual reproduction — is the highest of any known animal studied. This information helped Beye isolate, sequence and characterize the complementary sex determining gene location. Page and Beye were also able to knock out (turn off) an allele — or an alternative form of the same gene — and show how this could produce a male from a diploid genotype; work that was featured on the cover of the journal Cell in 2003.

However, the questions of which alleles — or gene variations — were key, how they worked together, in what combinations and why this system evolved, were left unanswered. This compelled the current team of collaborators to step back to review what actually constitutes an allele.

"There has to be some segment of that gene that is responsible in this allelic series, where if you have two different coding sequences in that part of the gene you end up producing a female," said Page, who is also the Foundation Chair of Life Sciences at ASU. "So we asked how different do two alleles have to be? Can you be off one or two base pairs or does it always have to be the same set of sequences? We came up with a strategy to go in and look at these 18-20 alleles and find out what regions of these genes are responsible among these variants."

"In this process, we also had to determine if there are intermediate kinds of alleles and discover how they might have evolved," said Page.

Tthe authors found that at least five amino acid differences can control allelic differences. Those 5 amino acid variations create femaleness through the complementary sex determiner (csd) gene — the master sex control switch.

"We discovered different amounts of arginine, serine and proline affect protein binding sites on the csd gene, which in turn lead to different conformational states, which then lead to functional changes in the bees — the switch that determines the shift from female to not female," said Page.

The authors also discovered a natural evolutionary intermediate step showing only three amino acid differences span the balance between female or not female.

These findings — taking nearly 200 years of study to pin down — suggest that incomplete sperm penetration may be the adaptive mechanism by which new molecular switches gradually evolved.

Some genes regulate phenotypes that are either present or absent. They are often important regulators of developmental switches and are involved in morphological evolution. We have little understanding of the molecular mechanisms by which these absence/presence gene functions have evolved, because the phenotype and fitness of molecular intermediate forms are unknown. Here, we studied the sex-determining switch of 14 natural sequence variants of the csd gene among 76 genotypes of the honeybee (Apis mellifera). Heterozygous genotypes (different specificities) of the csd gene determine femaleness, while hemizygous genotypes (single specificity) determine maleness. Homozygous genotypes of the csd gene (same specificity) are lethal [1,2,3,4,5,6]. We found that at least five amino acid differences and length variation between Csd specificities in the specifying domain (PSD) were sufficient to regularly induce femaleness. We estimated that, on average, six pairwise amino acid differences evolved under positive selection [7,8,9]. We also identified a natural evolutionary intermediate that showed only three amino acid length differences in the PSD relative to its parental allele. This genotype showed an intermediate fitness because it implemented lethality regularly and induced femaleness infrequently (i.e., incomplete penetrance). We suggest incomplete penetrance as a mechanism through which new molecular switches can gradually and adaptively evolve.

Martin Beye, Christine Seelmann, Tanja Gempe, Martin Hasselmann, Xavier Vekemans, M. Kim Fondrk, Robert E. Page

In addition to Beye and Page, authors included Christine Seelmann and Tanja Gempe with the University of Duesseldorf, Martin Hasslemann with the Institute of Genetics at the University of Cologne in Germany, Xavier Bekmans with Université Lille in France and Kim Fondrk with Arizona State University. The work was supported by grants from the Deutsche Forschungsgemeinschaft.

Provost Page is the Foundation Chair of Life Sciences at ASU, a professor in the School of Life Sciences and the author of "The Spirit of the Hive: The mechanism of social evolution" published by Harvard University Press in 2013.