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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Oct 21, 2013

 


Zebra finches learn to sing for social communication. Because their vocal learning process is similar with speech and language development in humans, the finch provides a useful model to study neural mechanisms underlying speech and language in humans.







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FOX P2 gene mutations linked to Autism

Zebra finches provide a useful model to study the neural mechanisms underlying speech and language in humans as research in the species links the FOXP2 gene, key to song development in the zebra finch, to similar human speech-language development in humans.

A study has shown for the first time how two tiny molecules regulate a gene implicated in speech and language impairments as well as autism disorders, and that social context of vocal behavior governs their function. The findings are published in the October 16, 2013 issue of The Journal of Neuroscience.

Speech and language impairments affect the lives of millions of people, but the underlying neural mechanisms are largely unknown and difficult to study in humans. Zebra finches learn to sing and use songs for social communications. Because the vocal learning process in birds has many similarities with speech and language development in humans, it provides a useful model to study neural mechanisms underlying speech and language in humans.

The research was led by Xiaoching Li, PhD, at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence (LSUHSC).

Mutations in the FOXP2 gene have been linked to speech and language deficits and in autism disorders. A current theory is that a precise amount of FOXP2 is required for the proper development of the neural circuits processing speech and language, so it is important to understand how the FOXP2 gene is regulated.

In this study, the research team identified two microRNAs, or miRNAs, – miR-9 and miR-140-5p – that regulate the levels of FOXP2. (MicroRNAs are a new class of small RNA molecules that play an important regulatory role in cell biology. They prevent the production of a particular protein by binding to and destroying the messenger RNA that would have produced the protein.)


The researchers showed that in the zebra finch brain, these miRNAs, miR-9 and miR-140-5p, are expressed in a basal ganglia nucleus required for vocal learning, and their function is regulated during vocal learning.

More intriguingly, the expression of these two miRNAs is also regulated by the social context of song behavior – in males singing undirected songs.


"Because the FOXP2 gene and these two miRNAs are evolutionarily conserved, the insights we obtained from studying birds are highly relevant to speech and language in humans and related neural developmental disorders such as autism," notes Xiaoching Li, PhD, LSUHSC Assistant Professor of Cell Biology and Anatomy as well as Neuroscience. "Understanding how miRNAs regulate FOXP2 may open many possibilities to influence speech and language development through genetic variations in miRNA genes, as well as behavioral and environmental factors."

Abstract
Mutations in the FOXP2 gene cause speech and language impairments, accompanied by structural and functional abnormalities in brain regions underlying speech-related sensory-motor processing, including the striatum and cerebellum. The sequence and expression patterns of FOXP2 are highly conserved among higher vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal nucleus required for vocal learning, and reduced FoxP2 expression impairs dendritic development and vocal learning. The FoxP2 gene encodes a transcription factor that controls the expression of many downstream genes. However, how FOXP2 gene expression is regulated is not clearly understood. miRNAs regulate gene expression post-transcriptionally by targeting the 3′-untranslated regions (UTRs) of mRNAs, leading to translational suppression or mRNA degradation. In this study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2 gene. We show that both miR-9 and miR-140-5p target specific sequences in the FoxP2 3′-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch brain is regulated during song development in juvenile zebra finches. We further show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X is regulated as a function of the social context of song behavior in males singing undirected songs. Our findings reveal a post-transcriptional mechanism that regulates FoxP2 expression and suggest that social vocal behavior can influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2 gene regulatory network.

The research team also included Zhimin Shi, PhD, and Lijuan Fu, PhD, from the LSU Health Sciences Center New Orleans Neuroscience Center, Zhide Fang, PhD, from the LSU Health Sciences Center New Orleans School of Public Health, and Guanzheng Luo, PhD, and XiuJie Wang, PhD, from the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences.

This research was supported by grants to LSUHSC's Dr. Li from the National Institutes of Health and the Brain Behavior Research Foundation.

LSU Health Sciences Center New Orleans educates Louisiana's health care professionals. The state's academic health leader, LSUHSC comprises a School of Medicine, the state's only School of Dentistry, Louisiana's only public School of Public Health, and Schools of Allied Health Professions, Nursing, and Graduate Studies. LSUHSC faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research in a number of areas in a worldwide arena, the LSUHSC research enterprise generates jobs and enormous economic impact. LSUHSC faculty have made lifesaving discoveries and continue to work to prevent, advance treatment, or cure disease.

Original press releas:http://www.eurekalert.org/pub_releases/2013-10/lsuh-lbs_1101713.php