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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
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Nkx2.1 downregulation is involved in brain abnormality induced by excess retinoic acid

Sansan Jia1,2, Li Zhang1, Kaili Zhang1

  • 1Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China.

Acta Biochimica Et Biophysica Sinica
|May 24, 2020
PubMed

Insights

Transcription factor Nkx2.1 is crucial for normal central nervous system (CNS) development. Silencing Nkx2.1 in mouse cells disrupts brain development by affecting the sonic hedgehog (Shh) signaling pathway.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Neural tube defects cause significant stillbirths, neonatal deaths, and lifelong disabilities.
  • Central nervous system (CNS) developmental abnormalities represent a substantial global health burden due to unknown causes.
  • Previous high-throughput transcriptome sequencing identified Nkx2.1 as a potential factor in brain development.

Purpose of the Study:

  • To investigate the role of transcription factor Nkx2.1 in brain abnormalities induced by excessive retinoic acid.
  • To elucidate the mechanism by which Nkx2.1 influences central nervous system development.

Main Methods:

  • In situ hybridization to determine Nkx2.1 expression patterns in the mouse brain.
  • Gene silencing of Nkx2.1 in mouse Neuro-2a (N2a) cells.
  • Assessment of cell proliferation and apoptosis following Nkx2.1 gene silencing.
  • Analysis of the sonic hedgehog (Shh) signaling pathway components in Nkx2.1-silenced cells.

Main Results:

  • Nkx2.1 is primarily expressed in the mouse brain.
  • Nkx2.1 gene silencing led to reduced proliferation and increased apoptosis in N2a cells.
  • Key components of the sonic hedgehog (Shh) signaling pathway were altered in Nkx2.1-silenced cells.

Conclusions:

  • Nkx2.1 plays a significant role in mouse brain development.
  • Nkx2.1 regulates central nervous system development, at least in part, through the sonic hedgehog (Shh) signaling pathway.

Keywords:
Nkx2.1apoptosisbrain abnormalityproliferationretinoic acid

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