Prenatal alcohol exposure is a leading cause of neurodevelopmental disability and may be accompanied by characteristic facial deficits caused, in part, by the apoptotic deletion of neural crest progenitor cells. The parent R01 (AA011085) tests the hypothesis that ribosome dysbiogenesis and nucleolar stress drive this apoptosis, based on our whole transcriptome analysis of these cells. Exon-level reanalysis of that dataset uncovered 19 miRNAs having altered representation in response to alcohol. One of these, miR- 3064-3p, is induced by alcohol (Fold-change 1.55, p=0.0002). miR-3064 is conserved across vertebrates and is implicated in our ribosome dysbiogenesis and calcium-mediated apoptosis. Dr. Olivia Rivera joined my lab July 22, 2019 to obtain training in epigenetics, and how alcohol dysregulates epigenetic signals to impede embryo development. Her Ph.D. identified a polymorphism in a zinc transporter that affects lactation in human and mouse. Upon discussion, we determined that investigation into miR- 3064?s role in neural crest apoptosis addresses this training, represents a logical extension of the parent award, and positions Dr. Rivera for an independent career in alcohol and epigenetics.

Public Health Relevance

Fetal alcohol spectrum disorders (FASD) are a leading cause of neurodevelopmental disability. Affected individuals may display a characteristic facial dysmorphology, and studies herein investigate the mechanism by which alcohol causes the apoptotic deletion of neural crest progenitors, a unique neuroprogenitor stem cell population that forms these facial structures. Findings address our knowledge gap in understanding that mechanism, and will inform why the early embryo and fetus is so vulnerable to the damaging effects of prenatal alcohol exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
3R01AA011085-23S1
Application #
10025955
Study Section
Program Officer
Murray, Gary
Project Start
2019-12-01
Project End
2023-02-28
Budget Start
2019-12-01
Budget End
2020-02-29
Support Year
23
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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