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Pregnancy Timeline by SemestersFemale Reproductive SystemFertilizationThe Appearance of SomitesFirst TrimesterSecond TrimesterThird TrimesterFetal 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 HemispheresEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterDevelopmental Timeline
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November 1, 2012--------News Archive Return to: News Alerts


In this cross section of the embryonic brain of a mouse, each color represents
the expression of a transcription factor in a specific head muscle.

Image courtesy of Oregon State University

WHO Child Growth Charts

       

Researchers Identify Genetic Basis of Cardiac, Craniofacial Birth Defects

A group of researchers in Israel, the United States and other nations have made important advances in the rapidly-expanding field of "regenerative medicine," outlining for the first time connections in genetic regulation that normally prevent birth defects in heart and facial muscles


Some of these problems are surprisingly common –
about 1 percent of all people have a congenital
heart defect. This basic research will provide
a road map to ultimately allow scientists
to grow the cell types needed to repair
such defects, from stem cells
that can be generated from
a person's own body.


The findings were published online today in the Proceedings of the National Academy of Sciences.

"Advances in regenerative medicine and developmental biology can now happen because we no longer require human embryos to generate stem cells," said Chrissa Kioussi, a co-author on the study and associate professor in the College of Pharmacy at Oregon State University. "The Nobel Prize this year was awarded to people who discovered how to make stem cells from adult biopsies."

Patient-derived stem cells can in principle be turned into any needed cell type, Kioussi said. The key is understanding the exact regulatory process than tells cells what type they are supposed to turn into, she said, such as a cell on the outside of the left ventricle of the heart.

"Once we understand these genetic controls in sufficient detail, we can not only turn a skin cell into a stem cell, but also turn that stem cell into the type needed for the patient to recover," Kioussi said. "We may eventually be able to grow replacement organs from the patient's cells."


In this study, researchers identified four specific
"transcription factor" genes that control processes
related to heart and head muscle formation.

When there are defects in this process, the result
can be death or a range of debilitating problems,
from cleft palate to facial malformations
and defective heart valves.

"There are about 20,000 genes in the human genome,
but only 2,000 of them describe transcription factors.
Transcription factors control the output of genes
– the genetic machinery – and collectively
determine which of the 20,000 possible
molecular machines is actually
deployed to make each particular cell type."

Chrissa Kioussi
co-author, associate professor
College of Pharmacy at Oregon State University


Scientists have found that these transcription factors don't work alone to define cell types in mammalian development – they function in small, self-stabilizing combinations of at least two or three.

The process moves rapidly after conception, and within one month most of the cells in the body "know" their cell type, based on the precise combination of transcription factors produced within them. When researchers understand how these stable transcription factor combinations get generated, they will know how to artificially generate these combinations in stem cells to convert them into the needed cell types.


Mammalian embryonic development is a process
of self construction, a series of transitions of
"temporary" cell types on the way to adult cell types.

A fertilized egg is essentially a stem cell
with the potential to become any other cell type.

At each intermediate stage, the "temporary"
cell types become more restricted in what
they can become, until they ultimately achieve
and maintain the adult type.


Kioussi: "In this work and in regenerative medicine, we care a great deal about all of these steps of cell differentiation. If you know all the steps it takes to get from here to there, you can identify what went wrong and find ways to fix it. This is being done already with some disease problems, and this work will move us closer to being able to repair heart and craniofacial defects."

The task is complex, Kioussi said, but very possible. Although there are 100 trillion cells in the human body, there are only about 100 adult cell types. Understanding and influencing the genetic specification of those cell types is possible and will probably revolutionize the treatment of many defects and diseases, Kioussi said.

This work was supported by the European Research Council, the Israel Science Foundation, the U.S. National Institutes of Health, and other agencies. The lead author was Eldad Tzahor at the Weizman Institute of Science in Israel, and other collaborators were from universities and agencies in the United Kingdom, India and Spain.

Editor's Note: A digital image of a cross-section of a mouse brain is available online: http://bit.ly/Tf60xO

Original article: http://www.eurekalert.org/pub_releases/2012-10/osu-rig102612.php