
Autism gene study finds widespread impact to brain's growth signaling network Mutations to Dyrk1a gene lead to brain undergrowth; an existing drug rescues the condition in newborn mice.
April 08, 2021
JUPITER, FL Damage to the autism-associated gene Dyrk1a, sets off a cascade of problems in developing mouse brains, resulting in abnormal growth-factor signaling, undergrowth of neurons, smaller-than-average brain size, and, eventually, autism-like behaviors, a new study from Scripps Research, Florida, finds.
The study from neuroscientist Damon Page, PhD, describes a new mechanism underlying the brain undergrowth seen in individuals with Dyrk1a mutations. Page's team used those insights to target the affected pathway with an existing medicine, a growth hormone. It restored normal brain growth in the Dyrk1a mutant mice, Page says.
As of now, there's simply no targeted treatments available for individuals with autism spectrum disorders caused by DYRK1A mutations, Page says. This represents a first step in evaluating a potential treatment that could be used in the clinic.
Their study appears Thursday in the journal Biological Psychiatry.
To track the effects of missing Dyrk1a genes, Jenna Levy, the paper's first author and a graduate student in Page's lab, engineered mice to have one or two broken copies of Dyrk1a in their developing brain tissue. The brains of both sets of mice developed abnormally, she found, displaying decreased brain size and number of neurons, as well as reduced number of other brain cells.
Downstream effects
The scientists also conducted unbiased proteomic studies, to see if the mutant mice had abnormally high or low levels of other unknown proteins that might impact brain development. Using a technique called high-resolution tandem mass spectrometry coupled to liquid chromatography, they found that the Dyrk1a mutant mice had reduced levels of 56 cellular proteins, and increased levels of 33. Many of those were known autism risk genes, some implicated in sending growth signals, Levy says.
The specific signaling cascades we found altered in Dyrk1a mutants are implicated in multiple causal mechanisms of autism, Levy says.
A computational biology technique called Ingenuity Pathway Analysis helped them find altered proteins. There were changes to those involved in nerve signaling, creation of synapses, and growth of axons, the long, insulated extensions that give neurons their distinct shape. Also, multiple forms of the protein Tau were depleted in the Dyrk1a mice.
These data implicate signaling cascades that were previously not known to be altered by Dyrk1a mutations, Page says.
Many autism genes
At least 200 different high-confidence risk genes for autism spectrum disorders have been identified, Page says, but little has been known about their roles and relationships, complicating diagnosis and treatment development efforts.
Page estimates that fewer than 1 percent of people diagnosed with autism spectrum disorder carry Dyrk1a mutations. Half of those show autistic behavioral traits, and about 70 percent have short stature. But many more people with autism diagnoses display microcephaly, or smaller-than-average head circumference, around 1 in 20, he says.
Importantly for treatment considerations, this study suggests there may be a point of convergence for multiple autism causes, Page says. Abnormal activity of this pathway appears to be shared across various genetic causes of autism, pointing to the possibility of common molecular target for therapeutics.
Previously, Page's lab has found autism-linked mutations to a gene called Pten can cause an opposite effect, brain overgrowth, or macrocephaly.
What we didn't know before is that the signaling disruptions that cause microcephaly, brain undergrowth, appear to be the flip side of the coin of the signaling disruptions that cause macrocephaly, brain overgrowth, Page says.
Because of that, they hypothesized that restoring growth signaling at a high level, using a known growth hormone, might rescue the brain undergrowth.
We thought that treating with insulin-like growth factor 1, IGF-1, should increase the activity of the downstream signaling cascade, which should result in increased growth, Levy says. After treating Dyrk1a mice from birth to day 7, she found that was the case. The observed microcephaly improved, and under the microscope, the brain tissue showed normalized neuron growth.
Toward targeted treatments
Based on those results, more investigation is warranted on the potential for growth hormone treatment to benefit a minority of children with autism, those with Dyrk1a mutations, or related downstream mutations and manifestations, including microcephaly, Page says.
Many questions remain. Whether IGF-1 treatment in the newborn Dyrk1a mice might also improve autism-like behaviors in the mice is still under investigation, Levy adds. Also, it's still unclear whether there is a critical treatment window during mouse brain development, and if so, how large that window may be.
In humans, neural progenitor cells begin forming in the third week of pregnancy. By the seventh week, actual neuron production starts. It's a short window neuron production in the billions is mostly finished by around the 20th week of gestation. As neurons are made, each migrates to its final destination in the forming brain. Once there, it starts making connections with other neurons, elongating and branching out, literally wiring the developing brain. Rapid brain development continues with experience and growth after birth.
Autism is a constellation of disorders with multiple causes, meaning that targeted, individualized treatments will be needed to assist people who seek them, Page says. Prevalence of autism diagnoses has been rising steeply since the 1990s. Research from
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
07/10/2026
Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
21/08/2026
A massive deployment of specialty cameras, graphics, and AR will showcase the na...
21/08/2026
The West Coast Conference unveiled its new 30-second public service announcement, the latest expression of the Conference's We Rise in the West brand iden...
21/08/2026
New look will serve as the foundation for ESPN's upcoming NFL season and Sup...
21/08/2026
ESPN will air the ninth annual MLB Little League Classic presented by New York Life on Sunday, August 23, at 7 p.m. ET from Historic Bowman Field in Williamspor...
21/08/2026
In an emotional acceptance speech in Canton, Grossman celebrated the pioneering ...
21/08/2026
Hardware-style timing shifts for software instruments
Following on from the release of Omniclock, Rapid Flow have launched a new sequencer plug-in that can ...
21/08/2026
Highly anticipated synthesizer ships in October 2026
Iceland-based Love Synthesizers have announced that their highly anticipated synthesizer is now availab...
21/08/2026
Masterpiece PBS The Forsytes has expanded its cast as its begins production in ...
21/08/2026
The BBC has unveiled first-look pictures from The Witch Farm, a new ghost story and mystery set in the Welsh countryside, coming soon to BBC iPlayer and BBC One...
21/08/2026
The BBC and BritBox have revealed the first look of Edward Bluemel as Hercule Poirot in the forthcoming six-part series Hercule from Mammoth Screen and Agatha C...
21/08/2026
Our priority was making the best, most powerful, most meaningful story possible,...
21/08/2026
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({ content_source:......
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Avid will unveil how it is transforming production to help media organizations unite content, agentic workflows, and business insights at IBC2026 (RAI Amsterda...
21/08/2026
New routing, modular processing, orchestration and monitoring capabilities bridge dedicated hardware and software-based processing as part of the Dynamic Media ...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
21/08/2026
When hundreds of thousands of people gather to hear a single voice, there is no room for compromise. Every word must be delivered clearly, every wireless transm...
21/08/2026
Telestream, a global leader in media workflow technologies, today announced a strategic partnership with ScorePlay, the AI-powered media infrastructure that spo...
21/08/2026
NUGEN Audio announces the launch of its new Post Plan and Producer Plan, two flexible subscription offerings designed to give audio professionals short term acc...
21/08/2026
Join the Screen Currency 2026 Ask Me Anything (AMA) Online 20 August 2026
(L-R): Adrian Coates, Grainne Brunsdon, Deirdre Brennan, Rachael Perkins
Got questio...
21/08/2026
** MEDIA ALERT **
VIZ Media Takes Over Anime NYC with BLEACH, BLACK TORCH, M...
21/08/2026
Tell us a little bit about your job I'm a Marketing Manager and work across a mix of clients and projects. No two days are ever quite the same, which defini...
21/08/2026
Beat The Lotto dives into the plot behind the 1980s National Lottery scandal
24 August 2026 at 9:35pm on RT One and RT Player
Beat The Lotto is the story o...
21/08/2026
The countdown to the most wonderful night of the year has officially begun!
Host Patrick Kielty is gearing up for another unforgettable Late Late Toy Show nig...
21/08/2026
Meet puppet duo Bellie and Whizz, who are about to explore all the big feelings ...
20/08/2026
From host-broadcaster and rightsholder support in June and July to MLS, NWSL, US...
20/08/2026
In-venue and creative video staffers at the professional and collegiate level ha...
20/08/2026
At IBC this year, Veritone (14.A56) is bringing two connected themes to the booth: architectural independence in enterprise AI, and the automation of the media ...
20/08/2026
Telestream and ScorePlay have announced a partnership combining Telestream's...
20/08/2026
The Grand Slam of Curling and Rock League have announced a three-year agreement with ESPN, bringing more than 300 hours of live curling coverage to U.S. audienc...
20/08/2026
Nielsen has announced a series of enhancements to its Big Data + Panel currency measurement methodology, taking effect August 31. The updates were developed in ...
20/08/2026
Net Insight has been selected by service provider Big Blue Marble (formerly ORS Group) to provide its Nimbra platform as the core media transport solution for a...
20/08/2026
The 2026 US Open will bring a series of free fan activations across New York City ahead of and during the tournament, which runs August 23-September 13.
We...
20/08/2026
Bridge Technologies will announce a transport stream (TS) playout feature for its VB330 and VB220 compressed monitoring probes at IBC2026 (Booth 1.A71).
The fe...
20/08/2026
ENCO will demonstrate solutions across captioning, translation, AI production tools, automation, and virtual production at IBC2026 (Stand 7.A34, Amsterdam RAI, ...
20/08/2026
MultiDyne Video and Fiber Optic Systems will demonstrate camera robotics and mot...
20/08/2026
Chyron will demonstrate news workflow solutions at IBC2026 (Stand 7.A23), marking the company's 60th anniversary. Highlights include updates to PRIME HTML, ...
20/08/2026
Spectrum SportsNet LA, the exclusive television home of the Los Angeles Dodgers, is now available to Spectrum customers in former Cox markets following the clos...
20/08/2026
swXtch.io will unveil expanded Global SRT Distribution and native multicast tran...
20/08/2026
Riedel Communications has announced that Transformation Church in the United States has deployed a communications system built around the Artist intercom ecosys...