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 March 31, 2014

 

Diagram of the GtaC shuttle and how it modifies gene expression during development.

(Top) Periodic nuclear enrichment by GtaC in response to cAMP waves.

(Bottom) In each cAMP cycle, GtaC transits through states of:

(green) nuclear active - promoting transcription
(blue) cytosolic
(red) nuclear inactive

Repeated cAMP stimulus leads to formation of gene products and their accumulation, which enables a cell to effectively count stimuli and modify gene expression in response.






WHO Child Growth Charts

 

 

 

Rhythmic signals synchronize all change in a cell

Waves of signals at the cellular level may explain not only how embryos grow, but how snails learn as well.

Johns Hopkins biologists have discovered that when biological signals hit cells in rhythmic waves, the cell's response can depend on the number of signaling cycles — not the strength or duration of that cycle. Because "oscillating signaling cycles" are common in many biological systems, the Hopkins scientists expect these findings in single-celled organisms will help explain the molecular phenomena of tissue and organ formation and fundamental forms of learning.

In a report to be published online in the journal Science, the investigators showed how repeated pulses of one signal on cells in an amoebae caused short bursts of activity in a specific gene, the products of that gene's activity lingered and built up with each pulse. The cumulative products ultimately changed the cell's fate.


"The mechanism we discovered here illustrates how a single cell can keep track of the number of times it has received a signal.

"In most signaling systems, the cellular response depends on the strength or duration of the signal. This system allows the cells to count."

Peter Devreotes, Ph.D., professor and director of the Department of Cell Biology


The Devreotes team figured out this signaling system using the amoeba Dictyostelium discoideum, a single-celled organism that will form into a multi-celled organism if threatened by starvation. At the heart of this process is a molecule called cAMP, a chemical released by starving cells in spurts — every six minutes — that is sensed by Dictyostelium discoideum amoeba nearby. The signal triggers other Dictyostelium discoideum amoeba to join together, specialize into new cell types, and become a complex organism.

Devreotes adds: "We have known since the 1970s that the cAMP signals achieve their best effect when they arrive every six minutes — not more and not less — but we had no idea why."

To find out, the Johns Hopkins team focused on the behavior of a regulatory protein called GtaC, which is similar to the human GATA - genes known to control stem cell fate in many tissues.


Amoebae that lack GtaC can't activate genes to cluster together more amoebae cells to specialise and build a multicellular structure.

Researchers attached GtaC to a green flourescent protein, then observed it enter the amoeba cell nucleus, leave the nucleus, then enter again, at a pace similar to cAMP — in six minute pulses.

If the cells were given a continuous supply of cAMP, after a brief lag, GtaC would leave the nucleus and remain outside for as long as cAMP was present.

When cAMP was removed, GtaC re-entered the nucleus.

Researchers then engineered GtaC to remain in the nucleus and found Dictyostelium discoideum amoeba cells began to group together and specialize prematurely. However, in amoeba cells without cAMP, these processes were not turned on — even with GtaC in the nucleus.


To better understand the role of GtaC, researchers inserted a protein that glows when GtaC turns on a particular gene. They then observed another rhythmic, six-minute pattern of activity. The glowing spots indicated gene activity peaks in intensity approximately every six minutes, and then lags about three minutes behind GtaC peak accumulation in the nucleus. According to Devreotes, this three-minute lag may reflect the time it takes for the gene to be turned on and the inserted glowing protein to be seen.

"It's likely that when GtaC is in the nucleus, it is in an inactive state, turning on genes only after receiving the cAMP signal. But as it has a very short window of time to work, the cAMP signal not only activates GtaC but also drives it out of the nucleus," says Huaqing Cai, Ph.D., a research associate in the Devreotes laboratory and the principle author on the paper.

Devreotes explains how the result of this system is that the total amount of gene activity in each cell depends entirely on the number of cycles it goes through and not on the total amount of cAMP received, or the length of time it was exposed to cAMP.

"The rhythmic reception of cAMP actually maximizes the activity of the developmental genes,"
he says. "It synchronizes the development of all of the cells in the population, like a conductor keeping time for the members of an orchestra."


"This system is similar to the simple electrical circuits in computers that enable them to count. But we think it could be sophisticated enough to explain more complex behaviors, like simple learning that depends on repeated stimulation.

Snails, for example, can learn to modify their behavior when a stimulus is administered repeatedly. This behavioral change lasts for several days and has been shown to involve changes in gene activity in the nerves of the snails. Continuous application of the stimulus does not induce the behavioral change, though.

So, as in the mechanism we have found here, the repeated on-again/off-again rhythm of the signal is crucial for eliciting the changes in gene expression."


Peter Devreotes, Ph.D.


The scientists believe that this signaling system may also explain some of the cell fate changes that occur during embryonic development.

Abstract
Biological oscillations are universally found in nature and are critical at many levels of cellular organization. In the social amoeba Dictyostelium discoideum, starvation-triggered cell-cell aggregation and the early stages of developmental morphogenesis are orchestrated by periodic extracellular cAMP (3',5'-cyclic adenosine monophosphate) waves, which provide both chemotactic cues and developmental signals. Repeated occupancy of G protein–coupled cAMP receptors promotes optimal gene expression, whereas continuous stimulation suppresses the program. Although this activity was recognized nearly 40 years ago, the underlying mechanism for the stimulus-response pattern has not been elucidated.

Conclusion
This work reveals a decoding mechanism by which oscillatory signals are used to guide gene expression and promote timely development. Tuning transcription to the number rather than the level of the external stimuli allows large populations of cells over an expanded territory to be developmentally synchronized. Similar mechanisms may operate in other circumstances where cellular plasticity is linked to repeated experience.

Other authors of the report include Yu Long of the Johns Hopkins University School of Medicine; Mariko Katoh-Kurasawa, Balaji Santhanam and Gad Shaulsky of the Baylor College of Medicine; Tetsuya Muramoto and Masahiro Ueda of RIKEN Quantitative Biology Center in Japan; and Lei Li of the University of Virginia.

This work was supported by grants from the National Institute of General Medical Sciences (GM 28007, GM 34933), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 039691), the Helen Hay Whitney Foundation, Japan Society for the Promotion of Science (KAKENHI 25840095) and RIKEN Incentive Research Projects.

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 March 31, 2014

 

Diagram of the GtaC shuttle and how it modifies gene expression during development.

(Top) Periodic nuclear enrichment by GtaC in response to cAMP waves.

(Bottom) In each cAMP cycle, GtaC transits through states of:

(green) nuclear active - promoting transcription
(blue) cytosolic
(red) nuclear inactive

Repeated cAMP stimulus leads to formation of gene products and their accumulation, which enables a cell to effectively count stimuli and modify gene expression in response.






WHO Child Growth Charts

 

 

 

Rhythmic signals synchronize all change in a cell

Waves of signals at the cellular level may explain not only how embryos grow, but how snails learn as well.

Johns Hopkins biologists have discovered that when biological signals hit cells in rhythmic waves, the cell's response can depend on the number of signaling cycles — not the strength or duration of that cycle. Because "oscillating signaling cycles" are common in many biological systems, the Hopkins scientists expect these findings in single-celled organisms will help explain the molecular phenomena of tissue and organ formation and fundamental forms of learning.

In a report to be published online in the journal Science, the investigators showed how repeated pulses of one signal on cells in an amoebae caused short bursts of activity in a specific gene, the products of that gene's activity lingered and built up with each pulse. The cumulative products ultimately changed the cell's fate.


"The mechanism we discovered here illustrates how a single cell can keep track of the number of times it has received a signal.

"In most signaling systems, the cellular response depends on the strength or duration of the signal. This system allows the cells to count."

Peter Devreotes, Ph.D., professor and director of the Department of Cell Biology


The Devreotes team figured out this signaling system using the amoeba Dictyostelium discoideum, a single-celled organism that will form into a multi-celled organism if threatened by starvation. At the heart of this process is a molecule called cAMP, a chemical released by starving cells in spurts — every six minutes — that is sensed by Dictyostelium discoideum amoeba nearby. The signal triggers other Dictyostelium discoideum amoeba to join together, specialize into new cell types, and become a complex organism.

Devreotes adds: "We have known since the 1970s that the cAMP signals achieve their best effect when they arrive every six minutes — not more and not less — but we had no idea why."

To find out, the Johns Hopkins team focused on the behavior of a regulatory protein called GtaC, which is similar to the human GATA - genes known to control stem cell fate in many tissues.


Amoebae that lack GtaC can't activate genes to cluster together more amoebae cells to specialise and build a multicellular structure.

Researchers attached GtaC to a green flourescent protein, then observed it enter the amoeba cell nucleus, leave the nucleus, then enter again, at a pace similar to cAMP — in six minute pulses.

If the cells were given a continuous supply of cAMP, after a brief lag, GtaC would leave the nucleus and remain outside for as long as cAMP was present.

When cAMP was removed, GtaC re-entered the nucleus.

Researchers then engineered GtaC to remain in the nucleus and found Dictyostelium discoideum amoeba cells began to group together and specialize prematurely. However, in amoeba cells without cAMP, these processes were not turned on — even with GtaC in the nucleus.


To better understand the role of GtaC, researchers inserted a protein that glows when GtaC turns on a particular gene. They then observed another rhythmic, six-minute pattern of activity. The glowing spots indicated gene activity peaks in intensity approximately every six minutes, and then lags about three minutes behind GtaC peak accumulation in the nucleus. According to Devreotes, this three-minute lag may reflect the time it takes for the gene to be turned on and the inserted glowing protein to be seen.

"It's likely that when GtaC is in the nucleus, it is in an inactive state, turning on genes only after receiving the cAMP signal. But as it has a very short window of time to work, the cAMP signal not only activates GtaC but also drives it out of the nucleus," says Huaqing Cai, Ph.D., a research associate in the Devreotes laboratory and the principle author on the paper.

Devreotes explains how the result of this system is that the total amount of gene activity in each cell depends entirely on the number of cycles it goes through and not on the total amount of cAMP received, or the length of time it was exposed to cAMP.

"The rhythmic reception of cAMP actually maximizes the activity of the developmental genes,"
he says. "It synchronizes the development of all of the cells in the population, like a conductor keeping time for the members of an orchestra."


"This system is similar to the simple electrical circuits in computers that enable them to count. But we think it could be sophisticated enough to explain more complex behaviors, like simple learning that depends on repeated stimulation.

Snails, for example, can learn to modify their behavior when a stimulus is administered repeatedly. This behavioral change lasts for several days and has been shown to involve changes in gene activity in the nerves of the snails. Continuous application of the stimulus does not induce the behavioral change, though.

So, as in the mechanism we have found here, the repeated on-again/off-again rhythm of the signal is crucial for eliciting the changes in gene expression."


Peter Devreotes, Ph.D.


The scientists believe that this signaling system may also explain some of the cell fate changes that occur during embryonic development.

Abstract
Biological oscillations are universally found in nature and are critical at many levels of cellular organization. In the social amoeba Dictyostelium discoideum, starvation-triggered cell-cell aggregation and the early stages of developmental morphogenesis are orchestrated by periodic extracellular cAMP (3',5'-cyclic adenosine monophosphate) waves, which provide both chemotactic cues and developmental signals. Repeated occupancy of G protein–coupled cAMP receptors promotes optimal gene expression, whereas continuous stimulation suppresses the program. Although this activity was recognized nearly 40 years ago, the underlying mechanism for the stimulus-response pattern has not been elucidated.

Conclusion
This work reveals a decoding mechanism by which oscillatory signals are used to guide gene expression and promote timely development. Tuning transcription to the number rather than the level of the external stimuli allows large populations of cells over an expanded territory to be developmentally synchronized. Similar mechanisms may operate in other circumstances where cellular plasticity is linked to repeated experience.

Other authors of the report include Yu Long of the Johns Hopkins University School of Medicine; Mariko Katoh-Kurasawa, Balaji Santhanam and Gad Shaulsky of the Baylor College of Medicine; Tetsuya Muramoto and Masahiro Ueda of RIKEN Quantitative Biology Center in Japan; and Lei Li of the University of Virginia.

This work was supported by grants from the National Institute of General Medical Sciences (GM 28007, GM 34933), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 039691), the Helen Hay Whitney Foundation, Japan Society for the Promotion of Science (KAKENHI 25840095) and RIKEN Incentive Research Projects.