Welcome to The Visible Embryo

 

 

Home-- -History-- -Bibliography- -Pregnancy Timeline- --Prescription Drugs in Pregnancy- -- Pregnancy Calculator- --Female Reproductive System- -Contact
 

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!



Home

History

Bibliography

Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System

Contact The Visible Embryo

News Alerts Archive

Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.
Content protected under a Creative Commons License.

No dirivative works may be made or used for commercial purposes.

 

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
Google Search artcles published since 2007
 
 

Home | Pregnancy Timeline | News Alerts |News Archive June 12, 2014

 

Left: Aboriginal boy with blond hair  Right: European girl with blond hair
"We think the genome is littered with [regulatory] switches. A little up or a little down
next to key genes–rather than on or off – is enough to produce significant differences.
The trick is to find which switches have changed to produce which traits."
David Kingsley, PhD




WHO Child Growth Charts

 

 

 

A single DNA tweak leads to blond hair

A single-letter change in our DNA genetic code is enough to generate blond hair in humans. Howard Hughes Medical Institute (HHMI) scientists have pinpointed that change, common in the genomes of Northern Europeans, and shown how it regulates an essential gene.

"This particular genetic variation in humans is associated with blond hair, but it isn't associated with eye color or other pigmentation traits," says David Kingsley, an HHMI investigator at Stanford University who led the study. "The specifici switch shows exactly how independent color changes can be encoded to produce specific traits in humans." Kingsley believes a handful of genes likely determine hair color in humans, however, the precise molecular basis of the trait was poorly understood.

He and his colleagues published their findings in the June 1, 2014, issue of the journal Nature Genetics.


Kingsley's discovery of the genetic hair-color switch didn't begin with a deep curiosity about golden locks. It began with his interest in fish.


For more than a decade, Kingsley has studied the three-spined stickleback, a small fish whose marine ancestors began to colonize lakes and streams at the end of the last Ice Age. By studying how sticklebacks have adapted to habitats around the world, Kingsley is uncovering evidence of the molecular changes that drive evolution.

In 2007 his team investigated how different populations of stickleback had acquired their skin colors and discovered changes in the same gene had driven changes in pigmentation in stickleback fish throughout the world. The team wondered if the same held true not just in stickleback evolution but among other species.


Genomic surveys by other groups had revealed that the gene—Kit ligand—is indeed evolutionarily significant among humans.

"The very same gene that we found controlling skin color in fish showed one of the strongest signatures of selection in different human populations around the world,"
says Kingsley. His team found that in humans, different versions of Kit ligand are associated with different skin colors.


Furthermore, in both fish and humans, the genetic changes associated with pigmentation differences are distant from the DNA that encodes the Kit ligand protein. Instead, they are in regions of the genome where regulatory sequences lie. A regulatory sequence of a nucleic acid molecule (DNA) is capable of increasing or decreasing the expression of specific genes from that molecule. Kingsley's subsequent stickleback studies have shown that when new traits evolve in different fish populations, changes in regulatory DNA are responsible about 85 percent of the time.

Genome-wide association studies link many human traits to changes in regulatory DNA, as well. Tracking down specific regulatory elements in the vast expanse of the genome can be challenging, however. So Kingsley's team focused its efforts on a human pigmentation trait that has long attracted attention in history, art, and popular culture.

Kit ligand encodes a protein that aids the development of pigment-producing cells, so it makes sense that changing its activity could affect hair or skin color. But the Kit ligand protein also plays a host of other roles throughout the body, influencing the behavior of blood stem cells, sperm or egg precursor cells, and neurons in the intestine. Kingsley wanted to know how alterations to the DNA surrounding this essential gene could drive changes in coloration without comprising Kit ligand's other functions.

Catherine Guenther, an HHMI research specialist in Kingsley's lab, began experiments to search for regulatory switches that might specifically control hair color. So, she snipped out segments of human DNA from regions implicated in previous blond genetic association studies, then linked each piece to a reporter gene that produces a telltale blue color when it is switched on. When she introduced these reporter genes into mice, she found that one piece of DNA switched on gene activity only in developing hair follicles. Examining the DNA in that regulatory segment, a single letter of the genetic code differed between individuals with different hair colors.

Preliminary experiments, conducted in cultured cells, indicated that placing the gene under the control of the "blond" switch reduced that gene's activity by about 20 percent, when compared to the "brunette" version of the same switch. This change seemed slight, but Kingsley and Guenther suspected they had identified a critical point in the DNA sequence.

They next engineered mice with a Kit ligand gene placed under the control of the brunette or the blond hair enhancer. Using technology developed by Liqun Luo, also an HHMI investigator at Stanford, they were able to ensure that each gene was inserted in precisely the same way, so that a pair of mice differed only by the single letter in their hair follicle switch—one carrying the ancestral version, the other carrying the blond version.


"Sure enough, when you look at them, that one base pair is enough to lighten the hair color of the animals, even though it is only a 20 percent difference in gene expression.

"This is a good example of how fine-tuned regulatory differences may be used to produce different traits. The genetic mechanism that controls blond hair doesn't alter the biology of any other part of the body. It's a good example of a trait that's skin deep—and only skin deep."

David Kingsley, HHMI investigator, Stanford University


Given Kit ligand's range of activities throughout the body, Kingsley believes many more regulatory elements are likely scattered throughout the DNA that surrounds a gene.


"We think the genome is littered with [regulatory] switches. A little up or a little down next to key genes–rather than on or off–is enough to produce significant differences. The trick is to find which switches have changed to produce which traits.

"Despite the challenges, we now clearly have the methods to link traits to particular DNA alterations. I think you will see a lot more of this type of study in the future, leading to a better understanding of both the molecular basis of human diversity and the susceptibility or resistance to many common diseases."

David Kingsley, PhD


Abstract
Hair color differences are among the most obvious examples of phenotypic variation in humans. Although genome-wide association studies (GWAS) have implicated multiple loci in human pigment variation, the causative base-pair changes are still largely unknown1. Here we dissect a regulatory region of the KITLG gene (encoding KIT ligand) that is significantly associated with common blond hair color in northern Europeans2. Functional tests demonstrate that the region contains a regulatory enhancer that drives expression in developing hair follicles. This enhancer contains a common SNP (rs12821256) that alters a binding site for the lymphoid enhancer-binding factor 1 (LEF1) transcription factor, reducing LEF1 responsiveness and enhancer activity in cultured human keratinocytes. Mice carrying ancestral or derived variants of the human KITLG enhancer exhibit significant differences in hair pigmentation, confirming that altered regulation of an essential growth factor contributes to the classic blond hair phenotype found in northern Europeans.

Return to top of page