Defective anorectal and urogenital malformations are some of the most severe congenital anomalies encountered in children. Only a few molecular cues have been identified in early formation of the female urogenital system. Here we describe a novel long non-coding RNA molecule known as Leat1 (long non-coding RNA, EphrinB2 associated transcript 1). This lncRNA is syntenic with EfnB2 (which encodes EphrinB2) and expressed during embryonic development of the genital tubercle. While lncRNAs have varied functions, many are known to regulate their neighbouring genes. Eph/Ephrin bidirectional signaling molecules mediate many patterning pathways in early embryonic development, including cloacal septation and urethral development. Here we investigate the role of Leat1 and its possible regulation of EphrinB2 during development of the female reproductive tract. We show that a loss of Leat1 leads to reduced EfnB2 expression in the developing female genital tubercle, reduced anogenital distance and decreased fertility.

肛门直肠和泌尿生殖器畸形是儿童中最严重的先天性畸形。在女性泌尿生殖系统的早期形成中仅发现了少数分子提示。在这里，我们描述了一种称为Leat1的新型长非编码RNA分子（长非编码RNA，与EphrinB2相关的转录本1）。该lncRNA与EfnB2（编码EphrinB2）同系，并在生殖结节的胚胎发育过程中表达。尽管lncRNA具有多种功能，但已知许多调节其邻近基因。Eph / Ephrin双向信号分子在早期胚胎发育中介导了许多模式化途径，包括泄殖腔分隔和尿道发育。在这里，我们研究了女性生殖道发育过程中的Leat1及其对EphrinB2的可能调节。我们显示，Leat1的缺失会导致发育中的女性生殖器结节中EfnB2的表达减少，肛门生殖器距离减少和生育力降低。