Genome complexity in embryology: directing construction (Introduction)

by David Turell , Monday, August 27, 2018, 19:43 (2280 days ago) @ David Turell

In this case legs:

https://phys.org/news/2018-08-fruit-flies-legs-molecular-mystery.html

"What do cancer and the growing legs of a fruit fly have in common? They can both be influenced by a single molecule, a protein that tends to call the shots inside of embryos as they develop into living, breathing animals. Present in virtually every creature on the planet, this protein goes by the name Epidermal Growth Factor Receptor protein, or EGFR.

"Now a team of neuroscientists at Columbia University has figured out how to tease apart the many roles EGFR plays in the body—challenging conventional wisdom in the process. They report their findings in PLOS Genetics.

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"EGFR signaling is woven into the fabric of development. It guides the formation of many body parts and has been an intense area of research focus for decades. Indeed, EGFR is so critical to development that disruptions to its normal activity likely play a role in everything from developmental disorders to Alzheimer's disease to cancer.

***

"the Columbia team tried a new approach. They focused on the EGFR ligands' many enhancers: small stretches of DNA that govern the ligands' activity and trigger EGFR activity in a precise manner in different parts of the body.

"'If you think of EGFR signaling as a soundboard, like what you'd find in a recording studio, enhancers are similar to the soundboard's knobs and dials," said Dr. Mann. "Just like turning those dials up or down changes the output of soundboard, turning up or down individual enhancers changes the ligand expression and, therefore, the resulting activity of signals."

"In this paper, the researchers first located the specific enhancers of the EGFR ligands that guided the fly's leg development. They then switched off only those enhancers.

"'In this way, we've managed to eliminate one small aspect of EGFR activity, leaving the rest of the signaling largely intact," said Dr. Mann.

"When doing so, they saw that the growth of the fly leg was not guided by a single source, the way a morphogen would act. Instead, the researchers found that EGFR sent signals from multiple different sources, located at different parts of the developing leg—knowledge made possible by the scientists' focus on enhancers.

"Because EGFR exists throughout the animal kingdom, these findings in the fly can be applied to studies of EGFR disruptions related to disease, such as developmental disorders and cancer."

Comment: this complex system did not develop by chance.