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Gene Review

Lhx3  -  LIM homeobox protein 3

Mus musculus

Synonyms: Homeobox protein LIM-3, Homeobox protein P-LIM, LIM/homeobox protein Lhx3, Lim-3, Lim3, ...
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High impact information on Lhx3

  • LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions [1].
  • Lhx3 is involved in the generation of two adjacent, but distinct, cell types for locomotion, motor neurons and V2 interneurons [1].
  • Thus, Lhx3 and Lhx4 act in a binary fashion during a brief period in development to specify the trajectory of motor axons from the neural tube [2].
  • Specification of pituitary cell lineages by the LIM homeobox gene Lhx3 [3].
  • The determination of all pituitary cell lineages, except the corticotrophs, was affected, suggesting that a distinct, Lhx3-independent ontogenetic pathway exists for the initial specification of this lineage [3].

Biological context of Lhx3


Anatomical context of Lhx3


Regulatory relationships of Lhx3

  • Furthermore, reprogramming the identity of limb-innervating motor neurons to that of dermomyotome-innervating MMCm cells using the LIM factor Lhx3 induces FGFR1 expression and shifts an increased number of motor axons to an FGF-responsive state [8].

Other interactions of Lhx3

  • Lhx3 and Lhx4 have redundant control over formation of the definitive pouch [4].
  • Thus, these experiments place Ptx1 upstream of Lim3/Lhx3 in a cascade of regulators that appear to work in a combinatorial code to direct pituitary-, lineage-, and promoter-specific transcription [9].
  • Furthermore, our data suggest that Hedgehog signaling, together with FGF8/10 signaling, synergizes to regulate expression of the LIM homeobox gene Lhx3, which has been proved to be essential for initial pituitary gland formation [10].
  • We show that OLPs originate in the ventral-most part of the Pax6-positive VZ, which at earlier times generates somatic (Isl2/Lim3-positive) MNs [11].
  • Previous studies have shown that Olig2 primes pMN cells to become motor neurons by triggering the expression of Ngn2 and Lhx3 [12].

Analytical, diagnostic and therapeutic context of Lhx3


  1. LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Thaler, J.P., Lee, S.K., Jurata, L.W., Gill, G.N., Pfaff, S.L. Cell (2002) [Pubmed]
  2. LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Sharma, K., Sheng, H.Z., Lettieri, K., Li, H., Karavanov, A., Potter, S., Westphal, H., Pfaff, S.L. Cell (1998) [Pubmed]
  3. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Sheng, H.Z., Zhadanov, A.B., Mosinger, B., Fujii, T., Bertuzzi, S., Grinberg, A., Lee, E.J., Huang, S.P., Mahon, K.A., Westphal, H. Science (1996) [Pubmed]
  4. Multistep control of pituitary organogenesis. Sheng, H.Z., Moriyama, K., Yamashita, T., Li, H., Potter, S.S., Mahon, K.A., Westphal, H. Science (1997) [Pubmed]
  5. Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke's pouch and increases cell apoptosis during mouse pituitary development. Zhao, Y., Morales, D.C., Hermesz, E., Lee, W.K., Pfaff, S.L., Westphal, H. Mech. Dev. (2006) [Pubmed]
  6. Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Lee, S.K., Pfaff, S.L. Neuron (2003) [Pubmed]
  7. The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitary. Seidah, N.G., Barale, J.C., Marcinkiewicz, M., Mattei, M.G., Day, R., Chrétien, M. DNA Cell Biol. (1994) [Pubmed]
  8. FGF as a target-derived chemoattractant for developing motor axons genetically programmed by the LIM code. Shirasaki, R., Lewcock, J.W., Lettieri, K., Pfaff, S.L. Neuron (2006) [Pubmed]
  9. The pan-pituitary activator of transcription, Ptx1 (pituitary homeobox 1), acts in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3. Tremblay, J.J., Lanctôt, C., Drouin, J. Mol. Endocrinol. (1998) [Pubmed]
  10. Hedgehog signaling is required for pituitary gland development. Treier, M., O'Connell, S., Gleiberman, A., Price, J., Szeto, D.P., Burgess, R., Chuang, P.T., McMahon, A.P., Rosenfeld, M.G. Development (2001) [Pubmed]
  11. Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. Sun, T., Pringle, N.P., Hardy, A.P., Richardson, W.D., Smith, H.K. Mol. Cell. Neurosci. (1998) [Pubmed]
  12. Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells. Lee, S.K., Lee, B., Ruiz, E.C., Pfaff, S.L. Genes Dev. (2005) [Pubmed]
  13. Linkage mapping of the gene for the LIM-homeoprotein LIM3 (locus Lhx3) to mouse chromosome 2. Mbikay, M., Tadros, H., Seidah, N.G., Simpson, E.M. Mamm. Genome (1995) [Pubmed]
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