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Overview

Lmx1b is member of Lmx subgroup of LIM-HD protiens, together with Lmx1a. Lmx1b is widely expressed in the developing mouse embryo, and it has a role in limb, eye, kidney, brain and skull development[1][2]. In the CNS, Lmx1b is required for formation of the isthmus, an important signaling center at the midbrain/hindbrain junction, where it maintains Wnt1 and Fgf8 expression[3][4][5]. Lmx1b is also required for hindbrain serotonergic and midbrain dopaminergic neuronal development[6][7][8]. It also controls roof plate formation[9] and differentiation and migration of a subset of dorsal dI3 inerneurons in the spinal cord[10]. In the developing limbs, Lmx1b coordinates the dorsoventral trajectories of incoming motor neurons[11]. Heterozygous mutations in human LMX1B cause nail patella syndrome, which is modeled by Lmx1b null mice which have limb and kidney abnormalities in addition to the CNS phenotypes outlined above[1].

References
  1. Chen H et al. Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat. Genet., 19(1):51-5. (PMID 9590288)
  2. Vogel A et al. Dorsal cell fate specified by chick Lmx1 during vertebrate limb development. Nature, 378(6558):716-20. (PMID 7501017)
  3. Adams KA et al. The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development, 127(9):1857-67. (PMID 10751174)
  4. Guo C et al. Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development, 134(2):317-25. (PMID 17166916)
  5. Matsunaga E et al. Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development. Development, 129(22):5269-77. (PMID 12399317)
  6. Ding YQ et al. Lmx1b is essential for the development of serotonergic neurons. Nat. Neurosci., 6(9):933-8. (PMID 12897786)
  1. Guo C et al. Lmx1b-controlled isthmic organizer is essential for development of midbrain dopaminergic neurons. J. Neurosci., 28(52):14097-106. (PMID 19109492)
  2. Zhao ZQ et al. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J. Neurosci., 26(49):12781-8. (PMID 17151281)
  3. Chizhikov VV and Millen KJ. Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J. Neurosci., 24(25):5694-703. (PMID 15215291)
  4. Ding YQ et al. Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord. Development, 131(15):3693-703. (PMID 15229182)
  5. Kania A et al. Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Cell, 102(2):161-73. (PMID 10943837)
Figures
FIGURE 1 Schematic of LIM-HD proteins
LIM-HD proteins are characterized by two protein binding LIM domains located N-terminal of DNA binding homeodomain. Within the Lmx group, amino acid sequence of the LIM domains are 64% and 84% identical, and the homeodomain is 100% identical.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.