Early embryology; brain development controls (Introduction)

by David Turell , Thursday, September 28, 2017, 17:37 (2613 days ago) @ David Turell

During early brain development modified mRNA's control development by their ability to produce a variety of proteins:

https://medicalxpress.com/news/2017-09-brain-birth-tightly-rna-modification.html

"A chemical tag added to RNA during embryonic development regulates how the early brain grows, according to research from the Perelman School of Medicine at the University of Pennsylvania.

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"In the last few years, scientists have discovered chemical modifications to messenger RNA (mRNA) across the genome at certain sites and found that these changes are dynamic, meaning that a specific chemical group is added and taken off by enzymes in a regular, patterned way. The chemical group studied in the Cell paper, m6A, is the most prevalent modification to mRNA in human cells.

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"The current thinking is that a tightly controlled molecular process guides the complicated development of the brain before birth—and that the process relies on a precise sequence of genes being turned on and off. However, even subtle mistakes in this process can become amplified later. Song likens this process to a train moving onto the wrong track and ending up miles and miles from its intended destination.

"The classic view of this control is that DNA codes for RNA, guiding which proteins will be made by cells. However, mRNA can be modified along the way so that it can produce proteins with many variations. A new field called epitranscriptomics was born out of this knowledge.
The Cell paper is the first study of epitranscriptomics in the embryonic mammalian brain, and the key is m6A, a marker for molecules bound for disposal within the cell. Normally, m6A-tagged mRNAs are related to such processes as cell replication and neuron differentiation, and m6A-tagging promotes their decay after they are no longer needed.

"If m6A is not added on the correct time schedule to a garbage-bound molecule, the developmental train goes down the wrong tracks. Ming and Song surmise that this is because developing brain cells get stuck at an earlier stage because the m6A cues for taking out the cellular trash are misread or not read at all.

"The researchers found that in a mouse model with depleted m6A, cell replication is prolonged, so that stem-cell differentiation, which normally reels out daughter cells in an orderly fashion, gets stuck. The knockout mouse develops less brain cells such as neurons and glia cells, and therefore has abnormal circuitry and a non-functioning brain.

"'We used an organoid, a mini-brain, made from human induced pluripotent stem cells to relate the mouse knockout findings to humans," Ming said. "m6A signaling also regulates neuron development in human forebrain organoids."

"Neuron development in the mini-brains that Ming has developed is similar to what happens in people, modeling fetal brain development up to the second trimester.

"'We were surprised when we found that human stem cells had a greater number of m6A tags compared to mouse cells," Ming said. "Comparing the m6A-mRNA landscapes between mouse and human embryonic brain development showed us that human-specific m6A-tagging might be related to brain-disorder risk genes.'"

Comment: Once again it is shown that planning and timing are very important in fetal development. I'm sure it is present in all organs, not just the brain, and strongly supports the obvious need for a designing mind setting up the whole process of embryology. The 'classic view' of DNA is out the window as this article points out. There are many layers of genomic control only some of which are known so far.