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Gene Review

Lmx1a  -  LIM homeobox transcription factor 1 alpha

Mus musculus

Synonyms: LIM homeobox transcription factor 1-alpha, LIM/homeobox protein 1.1, LIM/homeobox protein LMX1A, LMX-1.1, Lmx1.1, ...
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Disease relevance of Lmx1a

  • These data establish that Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease [1].
  • dreher is a spontaneous mouse mutation in which adult animals display a complex phenotype associated with hearing loss, neurological, pigmentation and skeletal abnormalities [2].
  • METHODS: By quantitative RT-PCR the sst subtype expression level was determined in human corticotroph adenomas [3].

High impact information on Lmx1a


Biological context of Lmx1a

  • Lmx1a also initiated a developmental program that drove an mdDA phenotype in mouse embryonic stem cells [5].
  • We demonstrate that the LIM homeodomain transcription factor, Lmx1a, mutated in the dreher mouse, acts to withdraw dorsal spinal cord progenitors from the cell cycle and simultaneously direct their differentiation into functional roof plate cells [6].
  • Targeted inactivation of Lbx1 leads to a severe reduction of neurones in the dorsal horn and to down-regulation of dorsal markers such as Lmx1a from E11.5 onwards [7].
  • The qc mutation is an autosomal recessive and has been mapped to the dr homologous region on rat chromosome 13, and Northern blot analysis demonstrated no expression of Lmx1a in qc/qc rats [8].
  • Positional cloning of the dreher locus demonstrated that an inactivating point mutation in the LIM homeodomain (HD) transcription factor encoded by the Lmx1a gene, is responsible for the dreher(J) phenotype [Nature, 403 (2000) 764] [9].

Anatomical context of Lmx1a

  • In a screen for homeobox transcription factors expressed in the embryonic ventral midbrain, Andersson et al. recently identified Lmx1a and Msx1 [5].
  • Control of roof plate formation by Lmx1a in the developing spinal cord [6].
  • Lmx1a cell-autonomously represses the dI1 progenitor fate, distinguishing the roof plate and dI1 interneuron programs, two major developmental programs of the dorsal neural tube [6].
  • Lmx1a is not directly involved in neural crest development [6].
  • We establish that Bmp signaling from epidermal ectoderm is necessary and sufficient for inducing Lmx1a and other co-factors that also regulate the extent of roof plate induction [6].

Associations of Lmx1a with chemical compounds

  • In contrast, in homozygous dreher mice, AChE activity in area CA3c of the hippocampus was not restricted to the stratum oriens, and extended upward into the infrapyramidal and suprapyramidal mossy fiber layers, the lower part of the stratum radiatum, the pyramidal cell layer, and downward toward the alveus [10].
  • Physiological responses to sst1 (CH-275) or sst2 (Octreotide) agonists were always correlated with the detection of respective sst mRNAs [11].

Regulatory relationships of Lmx1a

  • We conclude that Lmx1a controls multiple aspects of dorsal midline patterning and is a major mediator of early Bmp signaling in the developing spinal cord [6].

Other interactions of Lmx1a


Analytical, diagnostic and therapeutic context of Lmx1a

  • METHODS: Semiquantitative RT-PCR using sst-specific primers from mouse sequences was performed. sst(1) was localized using a polyclonal antiserum directed to human sst(1) in cryostat sections of retinas from either normal or optic nerve-transected animals [16].
  • These observations, together with other studies on the manipulation of sst expression, may help to optimise the uptake of radioligand in in vivo sst scintigraphy in humans and improve the potential effect of radiotherapy with radiolabelled (subtype-specific) SRIF analogues [17].


  1. Identification of intrinsic determinants of midbrain dopamine neurons. Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., Ericson, J. Cell (2006) [Pubmed]
  2. Dorsal patterning defects in the hindbrain, roof plate and skeleton in the dreher (dr(J)) mouse mutant. Manzanares, M., Trainor, P.A., Ariza-McNaughton, L., Nonchev, S., Krumlauf, R. Mech. Dev. (2000) [Pubmed]
  3. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Hofland, L.J., van der Hoek, J., Feelders, R., van Aken, M.O., van Koetsveld, P.M., Waaijers, M., Sprij-Mooij, D., Bruns, C., Weckbecker, G., de Herder, W.W., Beckers, A., Lamberts, S.W. Eur. J. Endocrinol. (2005) [Pubmed]
  4. The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Millonig, J.H., Millen, K.J., Hatten, M.E. Nature (2000) [Pubmed]
  5. Molecular programming of stem cells into mesodiencephalic dopaminergic neurons. Burbach, J.P., Smidt, M.P. Trends Neurosci. (2006) [Pubmed]
  6. Control of roof plate formation by Lmx1a in the developing spinal cord. Chizhikov, V.V., Millen, K.J. Development (2004) [Pubmed]
  7. The homeobox containing gene Lbx1 is required for correct dorsal-ventral patterning of the neural tube. Krüger, M., Schäfer, K., Braun, T. J. Neurochem. (2002) [Pubmed]
  8. Mutation at the Lmx1a locus provokes aberrant brain development in the rat. Kuwamura, M., Muraguchi, T., Matsui, T., Ueno, M., Takenaka, S., Yamate, J., Kotani, T., Kuramoto, T., Guénet, J.L., Kitada, K., Serikawa, T. Brain Res. Dev. Brain Res. (2005) [Pubmed]
  9. Roof plate and dorsal spinal cord dl1 interneuron development in the dreher mutant mouse. Millen, K.J., Millonig, J.H., Hatten, M.E. Dev. Biol. (2004) [Pubmed]
  10. Abnormal distribution of acetylcholinesterase activity in the hippocampal formation of the dreher mutant mouse. Sekiguchi, M., Nowakowski, R.S., Shimai, K., Huang, G., Inoue, T., Abe, H. Brain Res. (1993) [Pubmed]
  11. Somatostatin modulation of excitatory synaptic transmission between periventricular and arcuate hypothalamic nuclei in vitro. Lanneau, C., Peineau, S., Petit, F., Epelbaum, J., Gardette, R. J. Neurophysiol. (2000) [Pubmed]
  12. Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. Chizhikov, V.V., Millen, K.J. J. Neurosci. (2004) [Pubmed]
  13. Neuronal migration defects in the Dreher (Lmx1a) mutant mouse: role of disorders of the glial limiting membrane. Costa, C., Harding, B., Copp, A.J. Cereb. Cortex (2001) [Pubmed]
  14. Lhx9 and Lhx9alpha LIM-homeodomain factors: genomic structure, expression patterns, chromosomal localization, and phylogenetic analysis. Failli, V., Rogard, M., Mattei, M.G., Vernier, P., Rétaux, S. Genomics (2000) [Pubmed]
  15. Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6. Landsberg, R.L., Awatramani, R.B., Hunter, N.L., Farago, A.F., DiPietrantonio, H.J., Rodriguez, C.I., Dymecki, S.M. Neuron (2005) [Pubmed]
  16. Expression of somatostatin subtype 1 receptor in the rabbit retina. Cristiani, R., Fontanesi, G., Casini, G., Petrucci, C., Viollet, C., Bagnoli, P. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  17. Internalisation of isotope-coupled somatostatin analogues. Hofland, L.J., van Koetsveld, P.M., Waaijers, M., Lamberts, S.W. Digestion (1996) [Pubmed]
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