Alternative titles; symbols
HGNC Approved Gene Symbol: LHX1
Cytogenetic location: 17q12 Genomic coordinates (GRCh38) : 17:36,936,785-36,944,612 (from NCBI)
LIM genes, such as LHX1, constitute a large gene family whose gene products carry the LIM domain, a unique cysteine-rich zinc-binding domain. At least 40 members of this family have been identified in vertebrates and invertebrates, and are distributed into 4 groups according to the number of LIM domains and to the presence of domains such as homeodomains and kinase domains (summary by Bozzi et al., 1996).
Dong et al. (1997) cloned a cDNA encoding the 384-amino acid LIM1 polypeptide. LIM1 gene expression was detected in human brain, thymus, and tonsillar tissue. They also observed LIM1 expression in 58% of acute myelogenous leukemia (AML; 601626) cell lines studied and in 4 of 5 primary samples from chronic myeloid leukemia (CML; 608232) patients in myeloid blast transformation. The expression pattern and structural characteristics of the LIM1 gene suggested that it encodes a transcriptional regulatory protein involved in control of differentiation and development of neural and lymphoid cells.
Tsuchida et al. (1994) found that the combinatorial expression of 4 LIM genes, Isl1 (600366), Isl2 (609481), Lim1, and Lim3 (LHX3; 600577), in the developing embryonic chicken defined subclasses of motor neurons that segregated into columns in the spinal cord and selected distinct axonal pathways. These genes were expressed prior to the formation of distinct motor axon pathways and before motor columns appeared.
Kania et al. (2000) showed that Lim1 and Lmx1b (602575) control the initial trajectory of motor axons in the developing mammalian limb. The expression of Lim1 by a lateral set of lateral motor column (LMC) neurons ensured that their axons selected a dorsal trajectory in the limb. In a complementary manner, the expression of Lmx1b by dorsal limb mesenchymal cells was shown to control the dorsal and ventral axonal trajectories of medial and lateral LMC neurons. In the absence of these 2 proteins, motor axons appeared to select dorsal and ventral trajectories at random. Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory.
Nup133 (607613) and Seh1 (SEH1L; 609263) are components of the Y-complex subassembly of the nuclear pore complex scaffold and are required for mouse embryonic stem cell (mESC) survival during neuroectodermal differentiation. By transcriptomic and RT-PCR analyses, Orniacki et al. (2023) observed misregulated Nup210l (621033) and Lhx1 expression in Nup133 -/- mESCs during early stages of neuroectodermal differentiation. Mutation analysis revealed a requirement for the middle domain of Nup133 in mESC differentiation, nuclear basket assembly in neural progenitors, and regulation of the Nup210l and Lhx1 genes. A 4-fold reduction of Nup133 levels in mESCs affected nuclear basket assembly but had no effect on Nup210l or Lhx1 expression. Seh1-deficient neural progenitors also exhibited altered Nup210l and Lhx1 expression, but they had only a mild reduction in nuclear pore density. The authors concluded that Nup133 and Seh1 have a shared function in Nup210l and Lhx1 regulation during neuroectodermal differentiation that is independent of nuclear pore basket integrity.
Bozzi et al. (1996) determined the genomic structure of the human LHX1 gene, a member of the LIM/homeobox gene family. The transcript is assembled from 5 exons, which are separated by introns ranging in size from 93 bp to 2.3 kb. The 2 LIM domains are entirely contained in the first and second exons, while the homeodomain is split into exons 3 and 4. This structure closely parallels the organization of other mouse and human LHX genes whose genomic structure is known. An exception is the human ISL1 gene, whose homeodomain does not contain introns. Bozzi et al. (1996) noted that an intron at the same position also occurs in the XLIM1 gene as well as in other homeobox genes, such as EVX1 (142996) and EVX2 (142991). The authors suggested that the intron insertion in an ancestral homeobox was an ancient event predating the divergence of amphibians and mammals.
Dong et al. (1997) localized the human LHX1 gene to chromosome 11p13-p12 by fluorescence in situ hybridization.
Fujii et al. (1998) described the genomic organization of the mouse Lhx1 gene and its mapping to chromosome 11 in a region of homology to human chromosome 17q. This is obviously inconsistent with the mapping by Dong et al. (1997) to human chromosome 11p.
Gross (2024) mapped LHX1 the gene to chromosome 17q12 based on an alignment of the LXH1 sequence (GenBank BC101674) with the genomic sequence (GRCh38).
Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, Dorus et al. (2004) examined the evolution of genes involved in diverse aspects of nervous system biology. These genes, including LHX1, displayed significantly higher rates of protein evolution in primates than in rodents. This trend was most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution was most prominent in the lineage leading from ancestral primates to humans. Dorus et al. (2004) concluded that the phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development.
In the mouse the Lhx1 gene is expressed in the primitive streak and prechordal mesoderm and later in the developing kidney and portions of the central nervous system. By a knockout experiment, Shawlot and Behringer (1995) showed that Lhx1 is an essential regulator of the vertebrate head organizer.
Hukriede et al. (2003) studied the development of mouse and Xenopus embryos deficient in Lim1. They concluded that a primary function of Lim1 is to enable proper cell movements during gastrulation.
Bozzi, F., Bertuzzi, S., Strina, D., Giannetto, C., Vezzoni, P., Villa, A. The exon-intron structure of human LHX1 gene. Biochem. Biophys. Res. Commun. 229: 494-497, 1996. [PubMed: 8954926] [Full Text: https://doi.org/10.1006/bbrc.1996.1832]
Dong, W. F., Heng, H. H., Lowsky, R., Xu, Y., DeCoteau, J. F., Shi, X. M., Tsui, L. C., Minden, M. D. Cloning, expression, and chromosomal localization to 11p12-13 of a human LIM/HOMEOBOX gene, hLim-1. DNA Cell Biol. 16: 671-678, 1997. [PubMed: 9212161] [Full Text: https://doi.org/10.1089/dna.1997.16.671]
Dorus, S., Vallender, E. J., Evans, P. D., Anderson, J. R., Gilbert, S. L., Mahowald, M., Wyckoff, G. J., Malcom, C. M., Lahn, B. T. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119: 1027-1040, 2004. [PubMed: 15620360] [Full Text: https://doi.org/10.1016/j.cell.2004.11.040]
Fujii, T. A., Cvecklova, K., Gilbert, D. J., Copeland, N. G., Jenkins, d. A., Westphal, H. Genomic structure and chrosomal (sic) of the murine LIM class homeobox gene Lhx1. Mammalian Genome 9: 81-83, 1998. [PubMed: 9434953] [Full Text: https://doi.org/10.1007/s003359900686]
Gross, M. B. Personal Communication. Baltimore, Md. 12/12/2024.
Hukriede, N. A., Tsang, T. E., Habas, R., Khoo, P.-L., Steiner, K., Weeks, D. L., Tam, P. P. L., Dawid, I. B. Conserved requirement of Lim1 function for cell movements during gastrulation. Dev. Cell 4: 83-94, 2003. [PubMed: 12530965] [Full Text: https://doi.org/10.1016/s1534-5807(02)00398-2]
Kania, A., Johnson, R. L., Jessell, T. M. Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Cell 102: 161-173, 2000. [PubMed: 10943837] [Full Text: https://doi.org/10.1016/s0092-8674(00)00022-2]
Orniacki, C., Verrico, A., Pelletier, S., Souquet, B., Coulpier, F., Jourdren, L., Benetti, S., Doye, V. Y-complex nucleoporins independently contribute to nuclear pore assembly and gene regulation in neuronal progenitors. J. Cell Sci. 136: jcs261151, 2023. [PubMed: 37305998] [Full Text: https://doi.org/10.1242/jcs.261151]
Shawlot, W., Behringer, R. R. Requirement for Lim1 in head-organizer function. Nature 374: 425-430, 1995. [PubMed: 7700351] [Full Text: https://doi.org/10.1038/374425a0]
Tsuchida, T., Ensini, M., Morton, S. B., Baldassare, M., Edlund, T., Jessell, T. M., Pfaff, S. L. Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell 79: 957-970, 1994. [PubMed: 7528105] [Full Text: https://doi.org/10.1016/0092-8674(94)90027-2]