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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.

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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 Nov 25, 2013

 

The sea lamprey is an eel-like fish that regrows neurons linking its' brain to its' spinal cord.
It is not an eel at all. Lampreys have no jaws, and their skeleton is cartilaginous.

Image Credit: Cornell University.







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Nerve Regeneration Following Spinal Cord Injury

Fish, unlike humans, can regenerate nerve connections and recover normal mobility following an injury to their spinal cord.

Now, University of Missouri researchers have discovered how the sea lamprey, an eel-like fish, regrows the neurons that comprise the long nerve “highways” that link the brain to the spinal cord. Findings may guide future efforts to promote recovery in humans who have suffered spinal cord injuries.

The work appears in the journal Neuroscience.

“There is a lot of attention to why, following a spinal cord injury, neurons regenerate in lower vertebrates, such as the sea lamprey, and why they don’t in higher vertebrates, such as humans,” said Andrew McClellan, professor of biological sciences in the College of Arts and Science and director of the UM Spinal Cord Injury Research Program (SCIRP).


The study focuses on the regrowth of a particular group of nerve cells called reticulospinal neurons, which are necessary for locomotion.

These neurons are found in the hindbrain, or the brainstem, and send signals to the spinal cord of all vertebrates to control movements of the body, such as locomotor behavior.


When these nerve cells are damaged by a spinal cord injury, the animal is unable to move below the level of injury. While humans and other higher vertebrates would be permanently paralyzed, the sea lamprey and other lower vertebrates have the ability to regrow these neurons and recover the ability to move within a few short weeks.

In the study, McClellan and his colleagues isolated and removed injured reticulospinal neurons from sea lamprey and grew them in cultures. They applied chemicals that activated a group of molecules, called second messengers, to see what effects they had on these neurons’ growth.


The scientists discovered that activation of cyclic AMP, a molecule that relays chemical signals inside cells, acted somewhat like an “on” switch—essentially converting neurons from a non-growing state to a growing one. However, it had no effect on neurons that had already begun to grow.


McClellan says that the information learned from the study may shed light on studies of neural regeneration in mammals, including humans.


“In mammals, cyclic AMP does appear to enhance neural regeneration within the central nervous system in an environment that normally inhibits regeneration.

“Cyclic AMP seems to be able to overcome some of these inhibitory factors and promotes at least some regeneration. Hopefully our studies with the lamprey can provide a list of conditions that are important for neural regeneration to help guide therapies in higher vertebrates, and possibly in humans.”

Andrew McClellan, professor, biological sciences, College of Arts and Science, director University of Missouri Spinal Cord Injury Research Program (SCIRP).


Highlights
• cAMP stimulated neurite outgrowth of lamprey RS neurons in culture.
• Blockers of PKA inhibited neurite outgrowth of lamprey RS neurons.
• Forskolin, but not dbcAMP, altered the electrical properties of lamprey RS neurons.
• dbcAMP is a fully effective method to stimulate axonal regeneration of RS neurons.

Abstract
Reticulospinal (RS) neurons are critical for initiation of locomotor behavior, and following spinal cord injury (SCI) in the lamprey, the axons of these neurons regenerate and restore locomotor behavior within a few weeks. For lamprey RS neurons in culture, experimental induction of calcium influx, either in the growth cone or cell body, is inhibitory for neurite outgrowth. Following SCI, these neurons partially downregulate calcium channel expression, which would be expected to reduce calcium influx and possibly provide supportive conditions for axonal regeneration. In the present study, it was tested whether activation of second messenger signaling pathways stimulates neurite outgrowth of lamprey RS neurons without altering their electrical properties (e.g. spike broadening) so as to possibly increase calcium influx and compromise axonal growth. First, activation of cAMP pathways with forskolin or dbcAMP stimulated neurite outgrowth of RS neurons in culture in a PKA-dependent manner, while activation of cGMP signaling pathways with dbcGMP inhibited outgrowth. Second, neurophysiological recordings from uninjured RS neurons in isolated lamprey brain–spinal cord preparations indicated that dbcAMP or dbcGMP did not significantly affect any of the measured electrical properties. In contrast, for uninjured RS neurons, forskolin increased action potential duration, which might have increased calcium influx, but did not significantly affect most other electrical properties. Importantly, for injured RS neurons during the period of axonal regeneration, forskolin did not significantly alter their electrical properties. Taken together, these results suggest that activation of cAMP signaling by dbcAMP stimulates neurite outgrowth, but does not alter the electrical properties of lamprey RS neurons in such a way that would be expected to induce calcium influx. In conclusion, our results suggest that activation of cAMP pathways alone, without compensation for possible deleterious effects on electrical properties, is an effective approach for stimulating axonal regeneration of RS neuron following SCI.

Contributors to the study “Cyclic AMP stimulates neurite outgrowth of lamprey reticulospinal neurons without substantially altering their biophysical properties,” include Timothy Pale and Emily Frisch, MU Division of Biological Sciences.

The study was funded by the National Institutes of Health, the University of Missouri (UM) Spinal Cord Injury Research Program, UM Research Board and MU Research Council, and appeared in the journal Neuroscience.