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Gene Review

Lhx8  -  LIM homeobox protein 8

Mus musculus

Synonyms: L3, LIM homeobox protein 7, LIM/homeobox protein Lhx7, LIM/homeobox protein Lhx8, Lhx7
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Disease relevance of Lhx8

  • The cleft palate phenotype observed in Lhx8-mutant mice suggests that Lhx8 is a candidate gene for the isolated nonsyndromic form of cleft palate in humans [1].
  • Using the same set of reassortant viruses, the L1 (P = 0.00015) and L3 (P = 0.0065) genes were involved in differences of the ability of viral strains to grow in mouse L cells (fibroblasts), but the M1 gene (P = 0.12) was not [2].
  • To identify potential vaccine candidates for the prevention of infection with the filarial nematode Onchocerca volvulus, we screened an O. volvulus L3 stage cDNA library with sera from putatively immune (PI) subjects, and a prominent immunogenic clone of 1,184 nucleotides was identified [3].
  • By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2) [4].

Psychiatry related information on Lhx8


High impact information on Lhx8

  • In addition, we show that Lhx8 is downstream of Sohlh1 and critical in fertility [6].
  • Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8 [6].
  • Although cholinergic neurons are not formed, initial steps in their specification appear to be preserved, as indicated by a presence of cells expressing a truncated Lhx8 mRNA and mRNA of the homeobox gene Gbx1 [7].
  • The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain [7].
  • In addition, the number of cholinergic neurons is reduced in several other areas of the subcortical forebrain in Lhx8 mutants, including the caudate-putamen, medial septal nucleus, nucleus of the diagonal band, and magnocellular preoptic nucleus [7].

Biological context of Lhx8


Anatomical context of Lhx8

  • The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons [13].
  • Lhx8 was expressed in the dental mesenchyme between the bud and early bell stage of the molar tooth germ [8].
  • The present results suggest that Lhx8 plays an important role in the survival of mesenchymal cells of the tooth germ during development [8].
  • The genetic mechanisms that control development of these neurons suggest that most of them are derived from the basal telencephalon where Lhx8, a LIM-homeobox gene, is expressed [7].
  • Lhx8 mutants lack the nucleus basalis, a major source of the cholinergic input to the cerebral cortex [7].

Other interactions of Lhx8


Analytical, diagnostic and therapeutic context of Lhx8


  1. Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene lhx8. Zhao, Y., Guo, Y.J., Tomac, A.C., Taylor, N.R., Grinberg, A., Lee, E.J., Huang, S., Westphal, H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Identification of the viral genes responsible for growth of strains of reovirus in cultured mouse heart cells. Matoba, Y., Sherry, B., Fields, B.N., Smith, T.W. J. Clin. Invest. (1991) [Pubmed]
  3. Onchocerca volvulus glycolytic enzyme fructose-1,6-bisphosphate aldolase as a target for a protective immune response in humans. McCarthy, J.S., Wieseman, M., Tropea, J., Kaslow, D., Abraham, D., Lustigman, S., Tuan, R., Guderian, R.H., Nutman, T.B. Infect. Immun. (2002) [Pubmed]
  4. The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination. Ramachandran, S., Kumar, M.P., Rami, R.M., Chinnaiah, H.B., Nutman, T., Kaliraj, P., McCarthy, J. Microbiol. Immunol. (2004) [Pubmed]
  5. The homeobox genes Lhx7 and Gbx1 are expressed in the basal forebrain cholinergic system. Asbreuk, C.H., van Schaick, H.S., Cox, J.J., Kromkamp, M., Smidt, M.P., Burbach, J.P. Neuroscience (2002) [Pubmed]
  6. Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Pangas, S.A., Choi, Y., Ballow, D.J., Zhao, Y., Westphal, H., Matzuk, M.M., Rajkovic, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain. Zhao, Y., Marín, O., Hermesz, E., Powell, A., Flames, N., Palkovits, M., Rubenstein, J.L., Westphal, H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Expression and role of Lhx8 in murine tooth development. Shibaguchi, T., Kato, J., Abe, M., Tamamura, Y., Tabata, M.J., Liu, J.G., Iwamoto, M., Wakisaka, S., Wanaka, A., Kurisu, K. Arch. Histol. Cytol. (2003) [Pubmed]
  9. Structure and chromosomal localization of a murine LIM/homeobox gene, Lhx8. Kitanaka, J., Takemura, M., Matsumoto, K., Mori, T., Wanaka, A. Genomics (1998) [Pubmed]
  10. Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Grigoriou, M., Tucker, A.S., Sharpe, P.T., Pachnis, V. Development (1998) [Pubmed]
  11. Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7-deficient mice. Fragkouli, A., Hearn, C., Errington, M., Cooke, S., Grigoriou, M., Bliss, T., Stylianopoulou, F., Pachnis, V. Eur. J. Neurosci. (2005) [Pubmed]
  12. L3, a novel murine LIM-homeodomain transcription factor expressed in the ventral telencephalon and the mesenchyme surrounding the oral cavity. Matsumoto, K., Tanaka, T., Furuyama, T., Kashihara, Y., Mori, T., Ishii, N., Kitanaka, J., Takemura, M., Tohyama, M., Wanaka, A. Neurosci. Lett. (1996) [Pubmed]
  13. The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons. Mori, T., Yuxing, Z., Takaki, H., Takeuchi, M., Iseki, K., Hagino, S., Kitanaka, J., Takemura, M., Misawa, H., Ikawa, M., Okabe, M., Wanaka, A. Eur. J. Neurosci. (2004) [Pubmed]
  14. Comparison of the expression patterns of two LIM-homeodomain genes, Lhx6 and L3/Lhx8, in the developing palate. Zhang, Y., Mori, T., Takaki, H., Takeuch, M., Iseki, K., Hagino, S., Murakawa, M., Yokoya, S., Wanaka, A. Orthodontics & craniofacial research. (2002) [Pubmed]
  15. Fgf-8 determines rostral-caudal polarity in the first branchial arch. Tucker, A.S., Yamada, G., Grigoriou, M., Pachnis, V., Sharpe, P.T. Development (1999) [Pubmed]
  16. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function. Fragkouli, A., Stamatakis, A., Zographos, E., Pachnis, V., Stylianopoulou, F. Neuroscience (2006) [Pubmed]
  17. Differential expression of LIM-homeodomain genes in the embryonic murine brain. Matsumoto, K., Tanaka, T., Furuyama, T., Kashihara, Y., Ishii, N., Tohyama, M., Kitanaka, J., Takemura, M., Mori, T., Wanaka, A. Neurosci. Lett. (1996) [Pubmed]
  18. Type 3 reovirus neuroinvasion after intramuscular inoculation: viral genetic determinants of lethality and spinal cord infection. Mann, M.A., Tyler, K.L., Knipe, D.M., Fields, B.N. Virology (2002) [Pubmed]
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