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<p>The novel long non-coding RNA (lncRNA) <i>Leat1</i> is extraordinarily conserved in both its location (syntenic with <i>EfnB2</i>, an essential gene in anogenital patterning) and sequence. Here we show that <i>Leat1</i> is upregulated following the production of testosterone from the developing testis in mice and interacts with <i>EfnB2</i>, positively regulating its expression. <i>Leat1</i> expression is suppressed by estrogen, which in turn suppresses the expression of <i>EfnB2</i>. Moreover, the loss of <i>Leat1</i> leads to reduced <i>EfnB2</i>, resulting in a severe hypospadias phenotype. The human <i>LEAT1</i> gene is also co-expressed with <i>EFNB2</i> in the developing human penis, suggesting a conserved function for this gene in urethral closure. Together our data identify <i>Leat1</i> as a novel molecular regulator of urethral closure and implicate it as a target of endocrine disruption in the etiology of hypospadias.</p>

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A long non-coding RNA Leat1 mediates the hormone responsiveness of EfnB2 during male urogenital development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Deidre Mattiske,
  • Pascal Bernard,
  • Paul E. Gradie,
  • Richard R. Behringer,
  • Paul A. Overbeek,
  • Rachel J O’Neill,
  • Tiffany Phillips,
  • Melanie Stewart,
  • Neil Youngson,
  • Gerard Tarulli,
  • Andrew J. Pask

摘要

The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the production of testosterone from the developing testis in mice and interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis, suggesting a conserved function for this gene in urethral closure. Together our data identify Leat1 as a novel molecular regulator of urethral closure and implicate it as a target of endocrine disruption in the etiology of hypospadias.