Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR-NIRRH), Mumbai, India.
Sex Dev. 2022;16(2-3):147-161. doi: 10.1159/000518323. Epub 2021 Sep 10.
LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the LIM-HD proteins are regulated by the co-regulators LIM only (LMO) and LIM domain-binding (LDB). In the mouse genome, there are 13 LIM-HD genes (Lhx1-Lhx9, Isl1-2, Lmx1a-1b), 4 Lmo genes (Lmo1-4), and 2 Ldb genes (Ldb1-2). Amongst these, Lhx1 is required for the development of the müllerian duct epithelium and the timing of the primordial germ cell migration. Lhx8 is necessary for oocyte differentiation and Lhx9 for somatic cell proliferation in the genital ridges and control of testosterone production in the Leydig cells. Lmo4 is involved in Sertoli cell differentiation. Mutations in LHX1 are associated with müllerian agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. LHX9 gene variants are reported in cases with disorders of sex development (DSD). Mutations in LHX3 and LHX4 are reported in patients with combined pituitary hormone deficiency having absent or delayed puberty. A transcript map of the Lhx, Lmo, and Ldb genes reveal that multiple LIM-HD genes and their co-regulators are expressed in a sexually dimorphic pattern in the developing mouse gonads. Unraveling the roles of LIM-HD genes during development will aid in our understanding of the causes of DSD.
LIM 同源结构域 (LIM-HD) 家族基因是转录因子，在胚胎发育的多种功能中发挥着关键作用。LIM-HD 蛋白的活性受到 LIM 仅 (LMO) 和 LIM 结构域结合 (LDB) 共调节剂的调节。在小鼠基因组中，有 13 个 LIM-HD 基因 (Lhx1-Lhx9、Isl1-2、Lmx1a-1b)、4 个 Lmo 基因 (Lmo1-4) 和 2 个 Ldb 基因 (Ldb1-2)。其中，Lhx1 对于 Müllerian 管上皮的发育和原始生殖细胞迁移的时间至关重要。Lhx8 对于卵母细胞分化是必需的，而 Lhx9 对于生殖嵴中的体细胞增殖和 Leydig 细胞中睾酮的产生是必需的。Lmo4 参与支持细胞的分化。LHX1 的突变与 Müllerian 发育不全或 Mayer-Rokitansky-Kuster-Hauser (MRKH) 综合征有关。LHX9 基因变异在性发育障碍 (DSD) 病例中报道。LHX3 和 LHX4 的突变在患有垂体激素缺乏症的患者中报道，这些患者具有青春期缺失或延迟。Lhx、Lmo 和 Ldb 基因的转录图谱显示，多个 LIM-HD 基因及其共调节剂在发育中的小鼠性腺中以性二态的模式表达。揭示 LIM-HD 基因在发育过程中的作用将有助于我们理解 DSD 的原因。
