JAN 30, 2016

Genetic Control of the Notochord

WRITTEN BY: Kara Marker

Before the spinal cord, there is the notochord. Development of the notochord is essential for forming the nervous system and numerous other structures. In a new study from New York University, scientist Anna Di Gregorio and her team of researchers looked at Ciona species, also known as the sea squirt, to study the driving forces behind gene expression in the notochord.

Notochord cis-regulatory module (CRMs) control gene expression in the notochord, but no CRMs have ever been characterized in humans. Gregorio chose the Ciona for her study because of its “tractable notochord and simplified genome.”

For 14 Ciona notochord CRMs, Gregorio and her team studied the following:

Minimal sequences of DNA needed for function
Whether minimal notochord sequences are predictive of CRMs from the entire genome
How Ciona species differ in CRM sequence variety
How Ciona species differ in CRM sequence variety from other chordates (mice, zebrafish)

An unexpected observation has Gregorio excited about the potential to make her Ciona studies especially relevant to humans:

"While we were analyzing the CRMs of Ciona, we discovered that they are similar to notochord CRMs that had been previously identified in vertebrates," said Gregorio. "This finding is significant because it indicates that this research is not limited to Ciona but extends to other chordates, and most likely humans."

Their results also identified two transcription factors as binders of CRMs and as responsible for activating certain genes:

Brachyury
Foxa2

Again, these transcription factors were found in other chordates, like mice. Although the human genome is much more complex than that of Ciona, the results from Gregorio’s study are likely to carry over to her studies of human CRMs, which she plans to explore.

"The ability to identify mutations in notochord CRMs could enable us to predict the occurrence of birth defects, and eventually CRMs could be used as therapeutic targets to correct them," Gregorio said the implications for humans.

For more about the notochord in human development:

Source: New York University