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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development


Asynchronous waves key to embryo development

Researchers find wave like timing in stages of cell division act like a switch to regulate formation of the spine.

Cell division — known as mitosis — produces two identical daughter cells. It is a part of the cell cycle where chromosomes in a cell nucleus are separated into two identical groups, with each group ending up in its own nucleus. In general, mitosis is the division of the nucleus, and is often followed by cytokinesis, when the cytoplasm divides all it contains including organelles and cell membrane, into two new cells containing roughly equal shares of all of these components.

Mitosis is the basis of all early embryo development for sea squirts as well as for humans. When the embryo changes from being a highly synchronized ball of cells — to having distinct shapes within its structure, the first structure to form is the neural tube (in humans, our backbone — Carnegie Stage 7). However, researchers did not know what exactly controls the switch from synchronous to asynchronous cell pattern direction.

Recent research finds that pattern changes occur in waves of mitosis — each wave overlapping the other while passing back to the front over an embryo.

This wave follows the loss of the mitotic gap phase which typically begins four phases of the cell cycle.

The study was published in the journal Developmental Cell.

In order to grow, animal embryos must rapidly create more DNA through mitosis to increase their number and diversity of cells. Gap phases occur between cell cycles at the point of transition between phases: Gap 1 (G1) and Synthesis (S), Gap 2 (G2) and Mitosis (M). All phases are controlled by proteins such as cyclins and the enzyme Cdc25.

The simple nervous system of sea squirts (ascidians which are marine chordates, meaning they have a notochord or neural tube) are often used to model embryonic development in complex vertebrates. In ascidians, the embryo's outer layer of cells (its ectoderm) form a neural tube that joins together in a zipper-like motion moving from its "tail" to to its "head". But why and how does this happen?

Researchers fluorescently labeled one DNA replication protein in order to visually follow and analyze the timing of all the mitotic divions involved in creating and closing that neural tube. Using time-lapse pictures, they focused on the differences happening between the 10th and 11th mitotic cell cycles, and saw a unique G2-phase distinction occur.

"In the 11th cell cycle, the S-phase length increases in a posterior-to-anterior direction. This is responsible for the spatial pattern we saw.

"The S-phase length difference is identical in the 10th cell cycle, but then the length of the G2 phase progressively increases in a anterior-to-posterior direction, masking the asynchrony of the S phase.

"Compensation (or masking) is needed in development. When compensation is artificially removed, embryos fail to form proper neural tubes."

Yosuke Ogura, corresponding author

This change is apparently due to a decline in the amount (expression) of the Cdc25 protein — Cdc stands for "Cell Division Cycle"  — an enzyme that removes inhibitory phosphate residues controlling entry into and progression through various phases of the cell cycle.

The decline in the protein Cdc25, changes mitosis from a formerly posterior-to-anterior wave of cell divisions, to an anterior-to-posterior wave of cell divisions.

This reversal in direction causes cell layers to cover over each other, and ultimately "zipper" a furrow of cells developing along the middle of the elongating embryo. This furrow of cells is the neural tube - to become the backbone or notochord of that organism.

Without this counteracting mechanism, the 11th cycle of mitotic divisions would not promote morphogenesis — or the biological process which causes an organism to develop shape and distinguish specific cell functions.

Abstract Highlights
•The mitotic wave occurring during ascidian neurulation reflects S-phase asynchrony
•S-phase asynchrony is offset by compensatory asynchronous G2 phase until neurulation
•Mitotic timing controlled by a compensatory G2 phase is critical for morphogenesis
•Differential cdc25 expression, regulated by GATA and AP-2, governs G2-phase length

During neurulation of chordate ascidians, the 11th mitotic division within the epidermal layer shows a posterior-to-anterior wave that is precisely coordinated with the unidirectional progression of the morphogenetic movement. Here we show that the first sign of this patterned mitosis is an asynchronous anterior-to-posterior S-phase length and that mitotic synchrony is reestablished by a compensatory asynchronous G2-phase length. Live imaging combined with genetic experiments demonstrated that compensatory G2-phase regulation requires transcriptional activation of the G2/M regulator cdc25 by the patterning genes GATA and AP-2. The downregulation of GATA and AP-2 at the onset of neurulation leads to loss of compensatory G2-phase regulation and promotes the transition to patterned mitosis. We propose that such developmentally regulated cell-cycle compensation provides an abrupt switch to spatially patterned mitosis in order to achieve the coordination between mitotic timing and morphogenesis.

The article, "Developmental Control of Cell-Cycle Compensation Provides a Switch for Patterned Mitosis at the Onset of Chordate Neurulation" was published in Developmental Cell at DOI: http://dx.doi.org/10.1016/j.devcel.2016.03.013

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May 5, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

Overlapping, asynchronous waves dictate cell changes

A sea squirt embryo has synchronized cell divisions from its tail to its head until it reaches an
11th cell cycle of cell divisions. At that point, expression of protein from the Cdc25 gene drops.
This begins an asynchronous cycle of reversed head to tail cell divisions — overlapping previous
cell layers made tail to head. Eventually, the action of these tail to head, head to tail
directional reverses "zipper" close the neural tube or notochord of that animal.
Image Credit: University of Tsukuba, Japan





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