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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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July 18, 2012--------News Archive Return to: News Alerts


A blue tracer molecule was added to one of the two cells
formed at the first cell division of this tadpole.

The tracer continued to label exactly half of all subsequent cell divisions in the embryo,
illustrating that the very first cell division determines the midline of the animal.

Credit: Maria Lobikin, Tufts University.

WHO Child Growth Charts

       

Human Cells, Plants, Worms and Frogs Share Same Design for Organ Placement

As organisms develop, their internal organs arrange in a consistent asymmetrical pattern - heart and stomach to the left, liver and appendix to the right. But how?

Biologists at Tufts University have produced the first evidence that a class of proteins that make up a cell's skeleton - tubulin proteins - drives asymmetrical patterning across a broad spectrum of species, including plants, nematode worms, frogs, and human cells, at their earliest stages of development.

"Understanding this mechanism offers insights important to the eventual diagnosis, prevention and possible repair of birth defects that result when organs are arranged abnormally," said Michael Levin, Ph.D., senior author on the paper and director of the Center for Regenerative and Developmental Biology at Tufts University's School of Arts and Sciences.


"The research also suggests that
the origin of consistent asymmetry is ancient,
dating back to before plants and animals
became multicellular organisms."


Michael Levin


The work appears in the Proceedings of the National Academy of Sciences Online Early Edition publishing the week of July 16, 2012.

Tubulin Proteins Operate Across Species

Up to now, scientists have identified cilia—rotating hair-like structures located on the outside of cells—as having an essential role in determining where internal organs eventually end up. Scientists hypothesized that during later stages of development, cilia direct the flow of embryonic fluid which allows the embryo to distinguish its right side from its left.

But it is known that many species develop consistent left-right asymmetry without cilia being present, which suggests that asymmetry can be accomplished in other ways.

Levin's team pinpointed tubulin proteins, an important component of the cell's skeleton, or cytoskeleton. Tubulin mutations are known to affect the asymmetry of a plant called Arabidopsis, and Levin's previous work suggested the possibility that laterality is ultimately triggered by some component of the cytoskeleton. Further, this mechanism could be widely used throughout the tree of life and could function at the earliest stages of embryonic development.

In their latest experiment, the Tufts researchers injected the same mutated tubulins into early frog embryos. The resulting tadpoles were normal, except that their internal organs' positions were randomly placed on either the left or right side.

In subsequent experiments, collaborators at the University Of Illinois College Of Medicine and Cincinnati Children's Hospital Research Foundation found that mutated tubulins also have the same effect on left-right asymmetry of the nervous system in nematodes and on the function of human cells in culture.


Altogether, the Tufts experiment showed that tubulins
are unique proteins in the asymmetry pathway
that drive left-right patterning across
the wide spectrum of separated species.


Importantly, mutated tubulins perturbed asymmetry only when they were introduced immediately after fertilization, not when they were injected after the first or second cell division.

This suggested that a normal cytoskeleton drives asymmetry at extremely early stages of embryogenesis, many hours earlier than the appearance of cilia. Further, the Tufts biologists found that tubulins play a crucial role in the movement of other molecules to the left and right sides of the early embryo.

An Understanding of Birth Defects

Added Susan Haynes, Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the work: "What's remarkable about these findings is that the same proteins are involved in establishing asymmetry in organisms as diverse as plants, nematodes, and frogs, and they even affect symmetry in human tissue culture cells. This work is a great example of basic research that not only illuminates fundamental developmental mechanisms, but also increases our understanding of a class of serious human birth defects."

Other funding sources include the American Heart Association.
Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate, and professional programs across the university's schools is widely encouraged.

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