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 Dec 23, 2013

 

Mice carrying a mutation in the gene Foxc1 mimic sygnathia, a congenital disorder in which children are born with fused upper and lower jaws and related facial anomalies.

Image Credit: Courtesy of Dr. Kimberly Inman, Shawnee State University







WHO Child Growth Charts

 

 

 

First model of a human jaw defect - syngnathia

The face you critiqued in the mirror this morning was sculpted before you were born by a transient population of cells called neural crest cells. Those cells spring from neural tissue of the brain and embryonic spinal cord and travel throughout the body, where they morph into highly specialized bone structures, cartilage, connective tissue, and nerve cells.

Occasionally, neural crest cell development goes awry, causing birth defects affecting regions as diverse as the head, heart or gut. The way these conditions, known collectively as neurocristopathies, manifest themselves depends on the subset of neural crest cells involved: dysfunction in the population moving toward the face, for example, produces defects in the jaw, facial musculature, tongue, teeth, or palate, among others.


Given the importance of neural crest cells throughout the body, biologists have keenly studied the factors that are important for their formation, migration and maturation.

Now the lab of Paul Trainor, Ph.D., Investigator at the Stowers Institute for Medical Research, describes a paradigm in which neural crest cells are formed normally, migrate properly but mature incorrectly.


Published in the Dec. 19, 2013, issue of PLOS Genetics, the work characterizes a mutant mouse that mimics a congenital disorder known as syngnathia in which children are born with fused upper and lower jaws and related facial anomalies.

This finding offers hope for better understanding of syngnathia, which is a relatively rare disease, and other more common craniofacial diseases affecting jaw development. "Almost a third of all birth defects involve the head and face," says Trainor, noting that most can be blamed on problems relevant to neural crest cells. "Our primary motivation has always been to understand what causes them."

A molecular search by the Trainor lab identified genes required for correct neural crest migration or maturation. One candidate encodes a protein called Foxc1, expressed embryonically in mesodermal and neural crest cell tissues of the head, immediately adjacent to the developing pharynx.

Molecular geneticists typically evaluate what a gene does by eradicating or "knocking out" that gene in an animal and then observing what happens. To test Foxc1 function, Kim Inman, Ph.D., a former postdoctoral fellow in the Trainor lab and the study's first author, carefully analyzed the miniscule facial bones as well as facial cartilage of newborn Foxc1 "knock-out" mice using red and blue stains that distinguish the two.

"We immediately saw that components of the upper jaw were misshapen and fused to the lower jaw dentary bone," says Inman, noting that mice also showed abnormal facial muscles and poor formation of the temporomandibular joint, the hinge that allows the jaw to open and close. "When we see defects like this, we immediately suspect neural crest failure."

The study confirms these suspicions, with a surprising twist. When the team used mouse neural crest cell markers to visualize cells moving toward the embryonic head, they observed fairly normal migration. However, upon arrival at jaw-forming regions neural cells which would normally mature into bone-producing cell, now did so in inappropriate locations.


One interpretation of the new findings is that in normal animals Foxc1, which is a DNA-binding protein, regulates expression of factors that either shape facial soft tissues, block bone construction, or both.

In fact, the study builds a substantial case that one downstream signaling factor expressed in the embryonic jaw known as Fgf8 is just such a Foxc1 target. Thus, mice (and presumably humans) carrying a defective Foxc1 gene would display "syngnathic" traits due to loss of these signals.

The Trainor lab also focuses on neurocristopathies caused by impaired cell expansion or migration, such as a more common craniofacial disorder called Treacher Collins Syndrome, in which children exhibit small chins or jaws together with cleft palate, drooping eye slits and ear anomalies leading to hearing loss.


"In a condition like Treacher Collins we see a failure to make enough cells at the beginning of migration, while in syngnathia cells form properly but make bone in an inappropriate place due to loss of Foxc1," says Trainor. "This means there simply isn't going to be any one way to address all of these disorders. If you want to prevent or treat them you must understand how each originates cellularly and genetically."

Inman, now assistant professor of Natural Sciences at Shawnee State University in Portsmouth, Ohio, adds that craniofacial disorders carry a special stigma, one driven home by a sobering summary of over 50 human syngnathia case histories compiled for the study, the table lists the extent of jaw fusions and whether patients also showed cleft palate or tongue malformations. Some patients died in infancy, presumably from feeding disorders, while others survived thanks to surgical intervention.

"We need to devise new ways to treat craniofacial defects because of their tremendous medical need," she says. "But in this condition we are also talking about the face you present to the world. That face determines how you eat, talk, and interact with others. Having facial structures like everyone else is a tremendous part of who you are."

Abstract
Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the maxillary prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 – Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of other congenital craniofacial anomalies, including temporomandibular joint agenesis.

Author Summary
Approximately one-third of all babies born with congenital defects, exhibit malformations of the head and face. Anomalies can include cleft lip, cleft palate, and abnormal development of bones and muscles. Such defects result in significant infant mortality, as well as life-long physical and social consequences for patients. Improved repair and the development of prevention strategies requires a thorough understanding of the underlying genetic, molecular, and environmental factors that contribute to normal craniofacial development and the pathogenesis of disease. In this study, we report the first genetic model of syngnathia, a rare human craniofacial defect characterized by bony fusion of the upper and lower jaw. We discovered that Foxc1 is required for normal development of the bones and muscles of the jaw as well as the jaw joint. Our studies provide a mechanistic basis for understanding the cause of human syngnathia as well as the failure of jaw joint formation. Furthermore, our work enhances our knowledge of jaw development and may inform treatment strategies for patients with syngnathia and related craniofacial malformation conditions.

 


Other contributors include Tsutomu Kume, Ph.D., of the Feinberg School of Medicine at Northwestern University, who engineered the Foxc1 knock-out mice, and Patricia Purcell, Ph.D., of Boston Children's Hospital and Harvard Medical School, who provided markers and assessed bone structures in mutant mice.

The study was funded by the National Institute of Dental and Craniofacial Research (RO1 DE 016082), the March of Dimes, and the Stowers Institute for Medical Research.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over 900 million dollars in pursuit of its mission.

Currently, the Institute is home to nearly 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology-development and core facilities.