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Mouse Embryonic Lung Culture, A System to Evaluate the Molecular Mechanisms of Branching
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Sp3 is essential for normal lung morphogenesis and cell cycle progression during mouse embryonic development.

Alyssa M McCoy1,2, Omar Lakhdari1, Sayane Shome3,4

  • 1Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.

Development (Cambridge, England)
|February 10, 2023
PubMed
Summary

The transcription factor Sp3 is crucial for mouse development, regulating fetal cell differentiation and proliferation. Loss of Sp3 leads to perinatal death, abnormal lung development, and cell cycle arrest.

Keywords:
Alveolar developmentCell proliferationLipofibroblastLung mesenchymeMyofibroblastTranscriptional regulation

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Sp family transcription factors, including Sp1 and Sp3, regulate gene expression by binding GC boxes.
  • Sp3 exhibits dual roles in gene regulation, acting as both a repressor and activator.
  • Sp3 is essential for perinatal survival in mice.

Purpose of the Study:

  • To investigate the role of Sp3 in regulating murine fetal cell differentiation and proliferation.
  • To elucidate the molecular mechanisms underlying Sp3's impact on development.

Main Methods:

  • RNA sequencing (RNA-seq) was employed to analyze gene expression changes in Sp3-deficient cells.
  • Cellular phenotyping was conducted to assess developmental and morphological abnormalities.
  • Analysis of lung tissue structure and cell cycle progression in Sp3 knockout mice.

Main Results:

  • Sp3 knockout mice exhibited smaller size, perinatal lethality, and abnormal lung morphogenesis.
  • RNA-seq revealed altered extracellular matrix production, developmental signaling, and myofibroblast/lipofibroblast differentiation in Sp3-/- fetal lung mesenchymal cells.
  • Sp3 deficiency resulted in structural lung defects, including abnormal endothelial cells, impaired elastic fiber formation, and lipid droplet accumulation.
  • Sp3-/- cells and mice showed cell cycle arrest in G0/G1 phase with reduced expression of cell cycle regulators like Ccne1.

Conclusions:

  • Sp3 plays a critical role in regulating in vivo mouse gene expression and overall development.
  • Sp3 is essential for normal lung development, mesenchymal cell differentiation, and cell cycle progression.
  • The findings highlight the global impact of Sp3 on fetal development and cellular homeostasis.