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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
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Developmental Biology - Junk DNA

Stuttering DNA Orchestrates Start of Mosquito's Life

Junk DNA in mosquitoes repeats itself dozens of times, and is now shown to be essential to the early embryo...

Although this research specifically studied the yellow fever mosquito Aedes aegyptill — all organisms have DNA, the genetic material providing a blueprint for every aspect needed for life. The long double-helix-shaped DNA molecules in cells first translate DNA into RNA molecules — then RNA molecules reorganize into proteins, all to ensure functional systems develop throughout that organism's life.

But large parts of DNA do not make proteins. Called 'junk DNA', their function has remained unclear for a long time.
Now a certain type of junk DNA in mosquitoes, is found to repeat itself dozens of times. Known as 'satellite DNA', it plays an essential role in the early development of mosquito embryos.

Radboud University Medical Center scientists published their findings in the scientific journal Nature.

Early Development

All animals are composed of a variety of cell types that form different tissues and organs, originating from a single fertilized egg — a complex process. In order to ensure the fertilized egg successfully develops into an embryo, the mother not only provides half of the egg's hereditary DNA, she also gives extra proteins and RNA.

RNAs and proteins are essential, as these molecules direct the first cell divisions of the fertilized egg. Only after a number of cell divisions have taken place does the embryonic mosquito produce its own proteins and RNAs to promote future development.

Orchestrating RNAs
It turns out a certain piece of satellite DNA in the developing mosquito embryo is specifically responsible for breaking down maternal RNA.

In the laboratory of Professor Ronald van Rij, Rebecca Halbach (PhD candidate), discovered that stuttering DNA produces two small RNA molecules during the earliest stages of embryonic mosquito development. These small RNA molecules do not produce any protein, but bind to the mother's RNA molecules to help break them up.

Absent these 'regulatory RNAs' — further development of the embryo cannot continue.

Satellites and Dinosaurs
"During this study, we made some completely unexpected discoveries. Even though satellite DNA was first discovered sixty years ago, there was little known about its function. In this study we reveal how it actually has a very important function in a critical phase of development.

Together with researchers from Wageningen University, we examined a large group of mosquito species. This showed us that satellite DNA and specific regulatory RNAs originated around 200 million years ago, during the late Triassic period, an era coinciding with the rise of the dinosaurs.

It's great these small RNAs remained unchanged for so long. This specifically suggests they have an important function."

Ronald P. van Rij PhD, Associate Professor and head of the laboratory of Experimental Virology, Department of Medical Microbiology, University of Amsterdam.

From Mosquito to Human?

There are clear similarities between embryonic development in different animal species. But, there are large differences at the molecular level. This particular piece of stuttering DNA is not found in humans, although it is possible other satellite DNA plays a role in human embryonic development and/or in other animals.

An Accidental Discovery

The research builds upon an accidental discovery. Aedes aegypti is a mosquito that transmits important pathogens, such as dengue virus and Zika virus. Van Rij's research group examined how these types of viruses are transmitted by mosquitoes.
"We do a lot of research on the mosquito's immune system against viruses, as this immune system recognizes viral RNA and breaks it down into small fragments.

During an analysis of the RNA fragments in virus-infected cells, researchers Pascal Miesen and Rebecca Halbach accidentally stumbled upon small RNA molecules that do not come from the virus.

These small RNAs turn out to be produced by satellite DNA from within the cell."

Ronald P. van Rij PhD


Tandem repeat elements such as the diverse class of satellite repeats occupy large parts of eukaryotic chromosomes, mostly at centromeric, pericentromeric, telomeric and subtelomeric regions 1. However, some elements are located in euchromatic regions throughout the genome and have been hypothesized to regulate gene expression in cis by modulating local chromatin structure, or in trans via transcripts derived from the repeats 2,3,4. Here we show that a satellite repeat in the mosquito Aedes aegypti promotes sequence-specific gene silencing via the expression of two PIWI-interacting RNAs (piRNAs). Whereas satellite repeats and piRNA sequences generally evolve extremely quickly 5,6,7, this locus was conserved for approximately 200 million years, suggesting that it has a central function in mosquito biology. piRNA production commenced shortly after egg laying, and inactivation of the more abundant piRNA resulted in failure to degrade maternally deposited transcripts in the zygote and developmental arrest. Our results reveal a mechanism by which satellite repeats regulate global gene expression in trans via piRNA-mediated gene silencing that is essential for embryonic development.

Rebecca Halbach, Pascal Miesen, Joep Joosten, Ezgi Tasköprü, Inge Rondeel, Bas Pennings, Chantal B. F. Vogels, Sarah H. Merkling, Constantianus J. Koenraadt, Louis Lambrechts & Ronald P. van Rij.

The authors thank past and current members of the laboratory for discussions; A. B. Crist and A. Baidaliuk for their help with mosquito rearing and embryo injections; C. Bourgouin and N. Puchot for assistance with the microinjection apparatus; B. Dutilh for discussions about analyses of target-site enrichment; G. -J. van Gemert and M. Kristan for providing mosquitoes; and T. Möhlmann for collecting wild-caught mosquito samples. The following reagent was provided by the NIH/NIAID Filariasis Research Reagent Resource Center for distribution by BEI Resources, NIAID, NIH: Ae. aegypti, strain black eye Liverpool, eggs, NR-48921. Sequencing was performed by the GenomEast platform, a member of the France Génomique consortium (ANR-10-INBS-0009). This work is supported by a Consolidator Grant from the European Research Council under the European Union’s Seventh Framework Programme (grant number ERC CoG 615680) and a VICI grant from the Netherlands Organization for Scientific Research (grant number 016.VICI.170.090). A stay of R.H. at Pasteur Institute, Paris, France was supported by ERASMUS+.

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Apr 23 2020   Fetal Timeline   Maternal Timeline   News 

The Aedes aegypti mosquito is showing scientists that satellite (Junk) DNA repeats regulate gene
function via gene silencing — essential for embryonic development. CREDIT Hans Smid.

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