Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

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Neha Singh1, Domdatt Singh1, Anshul Bhide1

  • 1Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive and Child Health, Indian Council of Medical Research (ICMR), JM Street, Parel, Mumbai, 400012, India.

Experimental Cell Research
|March 26, 2022
PubMed

Insights

Lhx2 (LIM-homeobox gene 2) in female germ cells suppresses blood vessel formation in developing ovaries. Loss of Lhx2 leads to increased vascularization, suggesting a crucial role for germ cells in gonad development.

Area of Science:

  • Developmental Biology
  • Genetics
  • Reproductive Biology

Background:

  • LIM-homeobox genes are crucial for development, but their roles in gonadogenesis are not fully understood.
  • Lhx2, Ils2, Lmx1a, and Lmx1b exhibit sexually dimorphic expression in developing gonads across species.
  • Lhx2 shows female-biased expression in developing gonads and is specifically found in germ cells of mouse ovaries.

Purpose of the Study:

  • To investigate the role of Lhx2 in germ cells during gonad development.
  • To understand the molecular mechanisms underlying Lhx2's function in ovarian vascularization.

Main Methods:

  • Analysis of Lhx2 knockout XX mouse gonads.
  • Single-cell RNA sequencing (scRNA-seq) for gene expression profiling.
  • Transcriptome analysis to identify enriched pathways.
  • Gonad recombination assays to study cell migration.

Main Results:

  • Lhx2 knockout ovaries showed normal somatic cell development but enriched angiogenesis pathways.
  • Elevated pro-angiogenic factors and increased endothelial cell numbers were observed in Lhx2-/- ovaries.
  • Endothelial cell migration was ectopic and cell non-autonomous, forming an angiogenic network resembling testicular vasculature.
  • Lhx2 deficiency led to increased expression of male-biased endothelial cell genes in ovaries.

Conclusions:

  • Lhx2 in germ cells is essential for suppressing vascularization in the developing ovary.
  • Germ cells play a significant role in regulating vascular development within the gonads.
  • These findings highlight a novel function of germline-soma interactions in controlling gonad vascularization.
Keywords:
AngiogenesisEndothelial cell migrationGonad developmentHomeoboxLIM geneLIM-HDSex determinationTestisVasculature

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