Open AccessLIM Homeodomain (LIM-HD) Genes and Their Co-Regulators in Developing Reproductive System and Disorders of Sex Development
Author(s) -
Neha Singh,
Domdatt Singh,
Deepak Modi
Publication year - 2021
Publication title -
sexual development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 44
eISSN - 1661-5433
pISSN - 1661-5425
DOI - 10.1159/000518323
Subject(s) - biology , homeobox , gene , transcription factor , genetics , sexual differentiation , mullerian ducts , steroidogenic factor 1 , lim domain , germ cell , microbiology and biotechnology , disorders of sex development , zinc finger , uterus , nuclear receptor
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.