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Gene Review

Lhx2  -  LIM homeobox protein 2

Mus musculus

Synonyms: Homeobox protein LH-2, LH2A, LIM/homeobox protein Lhx2, Lh-2, Lim2, ...
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Disease relevance of Lhx2


High impact information on Lhx2

  • Bimodal Lhx2 regulation can be recapitulated in explants using two roof plate-derived signaling molecules, Bmp4 and Bmp2 [4].
  • Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway [4].
  • Here we show that cortical patterning involves regulation of the Lhx2 homeobox gene by the roof plate [4].
  • Here, using the yeast one-hybrid system and electrophoretic mobility shift assay, we report that Lhx2, a LIM-homeodomain protein, binds to the homeodomain site in the mouse M71 OR promoter region [5].
  • Moreover, the Lhx2(-/-) liver display a disrupted cellular organization and an altered gene expression pattern of the intrahepatic endodermal cells, and the increased deposition of ECM proteins precedes these abnormalities [1].

Biological context of Lhx2

  • Aberrant regional expression of early and late differentiation markers, taken together with unaltered region-restricted expression of the Msx1 homeobox gene in the progenitor cell layer of Lhx2-/- embryos, shows that Lhx2 function is not required for all aspects of regional specification of progenitors and neurons [6].
  • In order to explain the phenotype observed in Lhx2 mutant embryos, we previously proposed that an Lhx2 related gene might exist [7].
  • To address this we have analyzed gene expression from the Lhx2 locus during hepatic development in wild type and Lhx2(-/-) mice [8].
  • Targeted disruption of the LIM-homeobox gene Lhx2 has revealed that it is important for the expansion of the liver during embryonic development, whereas it appears not to be involved in the induction of hepatic fate [8].
  • Transfection of Lhx2 cDNA into a human HSC line down-regulates expression of genes characteristic of activated HSCs [1].

Anatomical context of Lhx2

  • Thus, these results indicate that a cell-autonomous function of Lhx2 is required for differentiation of progenitors into a heterogeneous population of individually and regionally specified mature olfactory sensory neurons [6].
  • Lhx9 is expressed in the pioneer neurons of the cerebral cortex, while Lhx2 is expressed throughout the cortical layers [7].
  • Lhx9 is closely related to Lhx2 and is expressed in the developing central nervous system (CNS) [7].
  • Conversely, strong divergences in expression patterns are observed between the telencephalon of the two species for Lhx1/5 and Lhx2/9 [9].
  • The hepatic cords subsequently migrate into and intermingle with the Lhx2+ cells of the septum transversum mesenchyme [8].

Associations of Lhx2 with chemical compounds

  • Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene [3].

Regulatory relationships of Lhx2

  • In adult liver the Lhx2+ mesenchymal cells co-express desmin, a marker associated with stellate cells [8].

Other interactions of Lhx2

  • Transcripts for multiple Dlx family members and Lhx2 were repeatedly detected in this screen [10].
  • The defects in optic vesicle development correlate with reduced expression of Chx10, which is also required for retina development; Rx, Lhx2, and Pax6 expression is not significantly affected [11].

Analytical, diagnostic and therapeutic context of Lhx2

  • Thus, Lhx2 immortalizes multipotent hematopoietic progenitor/stem cells that can generate functional progeny following transplantation into lethally irradiated hosts and can long-term repopulate stem cell-deficient hosts [12].


  1. Lhx2-/- mice develop liver fibrosis. Wandzioch, E., Kolterud, A., Jacobsson, M., Friedman, S.L., Carlsson, L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression. Richter, K., Pinto do O, P., Hägglund, A.C., Wahlin, A., Carlsson, L. Haematologica (2003) [Pubmed]
  3. Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene. Susa, T., Sato, T., Ono, T., Kato, T., Kato, Y. Biochim. Biophys. Acta (2006) [Pubmed]
  4. Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway. Monuki, E.S., Porter, F.D., Walsh, C.A. Neuron (2001) [Pubmed]
  5. The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons. Hirota, J., Mombaerts, P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Kolterud, A., Alenius, M., Carlsson, L., Bohm, S. Development (2004) [Pubmed]
  7. Characterization of Lhx9, a novel LIM/homeobox gene expressed by the pioneer neurons in the mouse cerebral cortex. Bertuzzi, S., Porter, F.D., Pitts, A., Kumar, M., Agulnick, A., Wassif, C., Westphal, H. Mech. Dev. (1999) [Pubmed]
  8. Lhx2 is expressed in the septum transversum mesenchyme that becomes an integral part of the liver and the formation of these cells is independent of functional Lhx2. Kolterud, A., Wandzioch, E., Carlsson, L. Gene Expr. Patterns (2004) [Pubmed]
  9. The LIM-homeodomain gene family in the developing Xenopus brain: conservation and divergences with the mouse related to the evolution of the forebrain. Bachy, I., Vernier, P., Retaux, S. J. Neurosci. (2001) [Pubmed]
  10. Expression of Dlx and Lhx family homeobox genes in fetal thymus and thymocytes. Woodside, K.J., Shen, H., Muntzel, C., Daller, J.A., Sommers, C.L., Love, P.E. Gene Expr. Patterns (2004) [Pubmed]
  11. Requirement for Mab21l2 during development of murine retina and ventral body wall. Yamada, R., Mizutani-Koseki, Y., Koseki, H., Takahashi, N. Dev. Biol. (2004) [Pubmed]
  12. Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo. Pinto do O, P., Richter, K., Carlsson, L. Blood (2002) [Pubmed]
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