LIM-homeodomain genes in mammalian development and human disease

Abstract

The human and mouse genomes each contain at least 12 genes encoding LIM homeodomain (LIM-HD) transcription factors. These gene regulatory proteins feature two LIM domains in their amino termini and a characteristic DNA binding homeodomain. Studies of mouse models and human patients have established that the LIM-HD factors are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. In this article, we review the roles of the LIM-HD proteins in mammalian development and their involvement in human diseases.

Expression of LHX3 and SOX2 during mouse inner ear development

“…Other members of the bHLH family, including NGN1 and NEUROD2, play a central role in sensoriepithelial and cochleovestibular ganglion development (Kim et al, 2001;Liu et al, 2000;Ma et al, 2000). LHX3 is involved in the differentiation of multiple cell types, including several neuronal subpopulations in the spinal cord and in the pituitary (Hunter and Rhodes, 2005;Shirasaki and Pfaff, 2002). The expression of LHX3 in the inner ear has not been extensively described (Sage et al, 2005).…”

“…LHX3 is involved in the regulation of differentiation of multiple cell types (Hunter and Rhodes, 2005;Shirasaki and Pfaff, 2002), but its expression in the inner ear has not been extensively described (Sage et al, 2005). LHX3 is expressed in vestibular and auditory hair cells shortly after they are generated by a wave of terminal mitoses.…”

A novel 12 bp deletion within goat <i>LHX4</i> gene significantly affected litter size

“…These hormones regulate growth and metabolism, reproductive development, and so on in humans and livestock (Mullena et al, 2007). Deficiency of the LHX4 and other genes (such as LHX3, and Pitx2) renders combined pituitary hormone deficiency (CPHD) and pituitary hypoplasia in both humans and mice (Raetzman et al, 2002;Hunter and Rhodes, 2005;Pfaeffle et al, 2008), suggesting that the LHX4 gene has a significant influence on stimulating the rapid proliferation of undifferentiated pituitary progenitors via activating LHX3 and maintaining expression of Pitx2 in mice (Gergics et al, 2015). Moreover, the mutations of the LHX4 gene are also associated with dominantly inherited GH deficiency.…”

Syndromic X-linked intellectual disability segregating with a missense variant in RLIM

“…9,13 RNF12 mainly localizes to the cell nucleus, 11 where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7 and REX1, by proteasomal degradation. 7,9,12,14 Thus, it modulates the activity of transcription factors, in particular those containing a LIM homeodomain, 15 and the formation of transcriptional multiprotein complexes. The ubiquitin system has a critical role in the remodeling of synapses and neurodevelopment, 16 and variants/CNV's in various E3 ubiquitin ligases may cause autism, [17][18][19] or both.…”