PMID- 32557641
OWN - NLM
STAT- MEDLINE
DCOM- 20210816
LR  - 20210816
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 44
IP  - 8
DP  - 2020 Aug
TI  - Transcriptome-Wide Regulation of Key Developmental Pathways in the Mouse Neural 
      Tube by Prenatal Alcohol Exposure.
PG  - 1540-1550
LID - 10.1111/acer.14389 [doi]
AB  - BACKGROUND: Early gestational alcohol exposure is associated with severe 
      craniofacial and CNS dysmorphologies and behavioral abnormalities during 
      adolescence and adulthood. Alcohol exposure during the formation of the neural 
      tube (gestational day [GD] 8 to 10 in mice; equivalent to4th week of human 
      pregnancy) disrupts development of ventral midline brain structures such as the 
      pituitary, septum, and ventricles. This study identifies transcriptomic changes 
      in the rostroventral neural tube (RVNT), the region of the neural tube that gives 
      rise to the midline structures sensitive to alcohol exposure during neurulation. 
      METHODS: Female C57BL/6J mice were administered 2 doses of alcohol (2.9 g/kg) or 
      vehicle 4 hours apart on GD 9.0. The RVNTs of embryos were collected 6 or 
      24 hours after the first dose and processed for RNA-seq. RESULTS: Six hours 
      following GD 9.0 alcohol exposure (GD 9.25), over 2,300 genes in the RVNT were 
      determined to be differentially regulated by alcohol. Enrichment analysis 
      determined that PAE affected pathways related to cell proliferation, p53 
      signaling, ribosome biogenesis, and immune activation. In addition, over 100 
      genes involved in primary cilia formation and function and regulation of 
      morphogenic pathways were altered 6 hours after alcohol exposure. The changes to 
      gene expression were largely transient, as only 91 genes identified as 
      differentially regulated by prenatal alcohol at GD 10 (24 hours postexposure). 
      Functionally, the differentially regulated genes at GD 10 were related to 
      organogenesis and cell migration. CONCLUSIONS: These data give a comprehensive 
      view of the changing landscape of the embryonic transcriptome networks in regions 
      of the neural tube that give rise to brain structures impacted by a 
      neurulation-stage alcohol exposure. Identification of gene networks dysregulated 
      by alcohol will help elucidate the pathogenic mechanisms of alcohol's actions.
CI  - (c) 2020 Research Society on Alcoholism.
FAU - Boschen, Karen E
AU  - Boschen KE
AUID- ORCID: 0000-0001-5838-0016
AD  - From the Bowles Center for Alcohol Studies, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - Ptacek, Travis S
AU  - Ptacek TS
AD  - Carolina Institute for Developmental Disabilities, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
AD  - UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA.
FAU - Simon, Jeremy M
AU  - Simon JM
AD  - Carolina Institute for Developmental Disabilities, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
AD  - UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA.
AD  - Department of Genetics, The University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA.
FAU - Parnell, Scott E
AU  - Parnell SE
AD  - From the Bowles Center for Alcohol Studies, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina, USA.
AD  - Department of Cell Biology and Physiology, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina, USA.
LA  - eng
GR  - F32 AA026479/AA/NIAAA NIH HHS/United States
GR  - P30 NS045892/NS/NINDS NIH HHS/United States
GR  - R01 AA026068/AA/NIAAA NIH HHS/United States
GR  - U01 AA021651/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200701
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Trp53 protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/genetics
MH  - Central Nervous System Depressants/*pharmacology
MH  - Cilia/genetics
MH  - Embryo, Mammalian/*drug effects/metabolism
MH  - Ethanol/*pharmacology
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Mice
MH  - Neural Tube/*drug effects/metabolism
MH  - Neurulation/*drug effects/genetics
MH  - Organelle Biogenesis
MH  - Pregnancy
MH  - RNA-Seq
MH  - Ribosomes/genetics
MH  - Tumor Suppressor Protein p53
PMC - PMC7484470
MID - NIHMS1615926
OTO - NOTNLM
OT  - Brain Development
OT  - Embryo
OT  - Fetal Alcohol Spectrum Disorders
OT  - Genes
OT  - Primary Cilia
EDAT- 2020/06/20 06:00
MHDA- 2021/08/17 06:00
PMCR- 2021/08/01
CRDT- 2020/06/20 06:00
PHST- 2020/03/18 00:00 [received]
PHST- 2020/05/02 00:00 [revised]
PHST- 2020/05/31 00:00 [accepted]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/08/17 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - 10.1111/acer.14389 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2020 Aug;44(8):1540-1550. doi: 10.1111/acer.14389. Epub 
      2020 Jul 1.