Featured Research

from universities, journals, and other organizations

Region, pathway found crucial for facial development in vertebrate embryos

Date:
July 17, 2014
Source:
Whitehead Institute for Biomedical Research
Summary:
A signaling pathway once thought to have little if any role during embryogenesis is a key player in the formation of the front-most portion of developing vertebrate embryos. Moreover, signals emanating from this region -- referred to as the “extreme anterior domain” (EAD) -- orchestrate the complex choreography that gives rise to proper facial structure.

Implanting beads coated with Bradykinin peptides prevents the abnormal facial phenotypes seen after loss of function in kininogen, part of the Kinin-Kallikreien pathway.
Credit: Courtesy Cell Reports

A signaling pathway once thought to have little if any role during embryogenesis is a key player in the formation of the front-most portion of developing vertebrate embryos. Moreover, signals emanating from this region—referred to as the “extreme anterior domain” (EAD)—orchestrate the complex choreography that gives rise to proper facial structure.

The surprising findings, reported by Whitehead Institute scientists this week in the journal Cell Reports, shed new light on a key process of vertebrate embryonic development.

“The results are exciting on a number of levels,” says Whitehead Member Hazel Sive. “We uncovered two new and important things about facial formation, and it turns out they tie together.”

Sive and her lab have long been using the frog Xenopus as a model in which to study development of the EAD into the mouth. Several years ago, Amanda Dickinson, a postdoctoral researcher at the time, and Sive showed that the Wnt signaling pathway, which is active throughout the body in a wide array of developmental processes and in cancer, is vital for mouth formation. At the time, they observed that frog embryos whose Wnt signaling was disrupted only in the EAD not only failed to develop mouths, but also experienced other facial abnormalities. This suggested that the EAD may act on adjacent regions as a craniofacial “organizer” or signaling center.

Intrigued by this possibility, the lab searched for regulatory factors in the EAD that could affect craniofacial formation as a whole. Microarray analysis pointed to three highly expressed genes that also happen to be active participants in the Kinin-Kallikrein signaling pathway, best known in humans for its roles in regulating blood pressure, inflammation, and kidney function.

“We had no inkling that this pathway was active in the embryo,” says Sive.

The lab confirmed its findings through a series of loss-of-function (LOF) experiments in which they knocked out the expression of each of the three genes in developing embryos and observed the effects. In all cases, the facial regions displayed significant defects, ranging from a lack of a mouth opening to the absence of nostrils to abnormally small eyes. In addition, the migration of the neural crest, whose cells give rise to the nerves, cartilage, bones, and other components of the face, failed to occur normally.

Because the expression of two of the pathway genes yields the peptide Bradykinin, the researchers theorized that introducing Bradykinin into LOF embryos at the appropriate stage would allow them to develop normally. They implanted tiny beads soaked with Bradykinin peptides, rescuing not only mouth formation but also proper neural crest development. The Kinin-Kallikrein pathway ultimately produces the signaling molecule nitric oxide (NO). Not surprisingly, the scientists found reduced NO levels in their LOF embryos. As they predicted, peptide-soaked beads led to an increase in NO production, further confirming the role of the pathway and its genes during facial formation. Importantly, NO had not been thought critical for development of this region.

Finally, in an effort to determine whether the requirement for Kinin-Kallikrein signaling in craniofacial development is conserved, Sive lab graduate student Justin Chen turned to LOF experiments in zebrafish. They found one of the pathway genes to be necessary for proper formation of both the mouth and the neural crest.

“This study greatly enhances our overall view of craniofacial development,” says Laura Jacox, a graduate student pursuing a dual DMD-PhD degree through the Harvard School of Dental Medicine and the Harvard-MIT Health Sciences and Technology program. “Knowing what tissues are communicating with each other may help us determine where we could intervene to prevent or treat developmental abnormalities of the face.”

Jacox is co-first author of the Cell Reports paper along with postdoctoral researcher Radek Sindelka, who now heads a research group in Prague, Czech Republic.

It is unclear whether similar mechanisms are at play in mammals, including humans. Sive, however, hints that there may be a connection. She notes that certain blood pressure medications, which act on parts of the Kinin-Kallikrein pathway, can cause severe craniofacial defects in newborns if taken during pregnancy. Although such defects have been attributed to effects mediated by the kidneys, Sive’s latest findings may implicate Kinin-Kallikrein signaling.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Matt Fearer. Note: Materials may be edited for content and length.


Journal Reference:

  1. Laura Jacox, Radek Sindelka, Justin Chen, Alyssa Rothman, Amanda Dickinson, Hazel Sive. The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.06.026

Cite This Page:

Whitehead Institute for Biomedical Research. "Region, pathway found crucial for facial development in vertebrate embryos." ScienceDaily. ScienceDaily, 17 July 2014. <www.sciencedaily.com/releases/2014/07/140717124528.htm>.
Whitehead Institute for Biomedical Research. (2014, July 17). Region, pathway found crucial for facial development in vertebrate embryos. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/07/140717124528.htm
Whitehead Institute for Biomedical Research. "Region, pathway found crucial for facial development in vertebrate embryos." ScienceDaily. www.sciencedaily.com/releases/2014/07/140717124528.htm (accessed October 20, 2014).

Share This



More Plants & Animals News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Captive Dolphin Gives Birth

Captive Dolphin Gives Birth

Reuters - Light News Video Online (Oct. 20, 2014) SeaWorld in San Diego welcomes a new bottlenose dolphin, the second calf for 13-year-old female, Sadie. Rough Cut. (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
White Rhino's Death In Kenya Means Just 6 Are Left

White Rhino's Death In Kenya Means Just 6 Are Left

Newsy (Oct. 20, 2014) Suni, a rare northern white rhino at Ol Pejeta Conservancy, died Friday. This, as many media have pointed out, leaves people fearing extinction. Video provided by Newsy
Powered by NewsLook.com
Fish Fossil Shows First-Ever Sex Was Done Side By Side

Fish Fossil Shows First-Ever Sex Was Done Side By Side

Newsy (Oct. 19, 2014) A 380-million-year-old fish may be the first creature to have copulative sex - and it was side by side with arms linked, like square dancers. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins