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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
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Home | Pregnancy Timeline | News Alerts |News Archive Jan 9, 2014

 

Human blood cells, similar to embryonic and nerve cells, can extend thin
and very long extensions called cytonemes, along a length of 50 to 100 cells.

Image Credit: František Baluška, Landes Bioscience






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Animal cells communicate by reaching and touching

In a finding that directly contradicts the standard biological model of animal cell communication, UCSF scientists have discovered that typical cells in animals have the ability to transmit and receive biological signals by making physical contact with each other, even at long distance.

This mechanism is similar to the way neurons communicate with other cells, but is in contrast to the standard belief that non-neuronal cells "basically spit out signaling proteins into extracellular fluid and hope they find the right target," explained senior investigator Thomas B. Kornberg, PhD, a professor of biochemistry with the UCSF Cardiovascular Research Institute.

The paper was published on January 2, 2014 in the journal Science.

Working with living tissue from Drosophila – fruit flies – Kornberg and his team demonstrated that cells send out long, thin tubes of cytoplasm called cytonemes, which Kornberg said "can extend across the length of 50 or 100 cells" before touching the cells they are targeting.


The point of contact between a cytoneme and its target cell acts as a communications bridge between two cells.


Says Kornberg: "It's long been known that neurons communicate in a similar way – by transferring signals at points of contact called synapses, and transmitting a response over long distances in long tubes called axons. However, it's always been thought that this mode of signaling was unique to neurons.


"We have now shown that many types of animal cells have the same ability to reach out and synapse with one another in order to communicate, using signaling proteins as units of information instead of the neurotransmitters and electrical impulses that neurons use."

Thomas B. Kornberg, PhD, senior investigator and professor of biochemistry with the UCSF Cardiovascular Research Institute


In fact, adds Kornberg, "I would argue that the only strong experimental data that exists today for a mechanism by which these signaling proteins move from one cell to another is at these points of contact and via cytonemes."

However, he noted, "There are 100 years worth of work and thousands of scientific papers in which it has been simply assumed that these proteins move from one cell to another by moving through extracellular fluid. So this is a fundamentally different way of considering how signaling goes on in tissues."

Working with cells in the Drosophila wing that produce and send the signaling protein Decapentaplegic (Dpp), Kornberg and his team showed that Dpp transfers between cells at the sites where cytonemes form a connection, and that cytonemes are the conduits that move Dpp from cell to cell.

The scientists discovered that the sites of contact have characteristics of synapses formed by neurons. They demonstrated that in flies that had been genetically engineered to lack synapse-making proteins, cells are unable to form synapses or signal successfully.


"In the mutants, the signals that are normally taken up by target cells are not taken up, and signaling is prevented. This demonstrates that physical contact is required for signal transfer, signal uptake and signaling."

Thomas B. Kornberg, PhD, senior invesiator, and professor of biochemistry with the UCSF Cardiovascular Research Institute


Kornberg said that a major reason that animal cell cytonemes had not been observed or studied previously is because these structures are too fragile to survive traditional laboratory methods of preparing cells for imaging.

"During the last decade or so, though, there have been fantastic technical advances, including new techniques in genetic engineering, new microscopes that improve the resolution and sensitivity for imaging living cells and the development of fluorescent marker proteins that we can attach to proteins of interest."

Using these new technologies, Kornberg and his team have captured vivid images, and even movies, of fluorescent signaling proteins moving through fluorescently marked cytonemes.


"We are not saying that cells always use cytonemes for signaling. Hormones, for example, are another method of long distance cell signaling. A cell that takes up insulin does not care where that insulin came from – a pancreas or an intravenous injection.

"But there are signals of a specialized type, such as those that pass between stem cells and the cells around them, or signals that determine tissue growth, patterning and function, where the identity of the communicating cells must be precisely defined. It's important that these signals are received in the context of the cells that are making them."

Thomas B. Kornberg, PhD


Kornberg noted that other research teams have made observations that suggest that cytoneme-based signaling may also occur "between stem cells and the cells that instruct them on what they are going to do and where they are going to go." He believes cancer cells may also use this method to communicate with their neighbors.

The discovery of animal cell cytonemes and the critical role they play in long distance signaling "opens up a wonderful biology of which we have very little understanding, at this point," said Kornberg. "For example, how do these cytonemes find their targets? How do they know when they have found them? These are some of the questions we are still pursuing."

Abstract
Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target; and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses.

Authors
Sougata Roy, Hai Huang, Songmei Liu, Thomas B. Kornberg

Co-authors of the study are Sougata Roy, PhD, Hai Huang, PhD and Songmei Liu of UCSF.

The study was supported by funds from the National Institutes of Health (K99HL114867 and GM030637).

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.