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

• Thereafter, Lhx3 and Lhx4 together regulate proliferation and differentiation of pituitary-specific cell lineages [4].
• Thus, Lhx3 and Lhx4 dictate pituitary organ identity by controlling developmental decisions at multiple stages of organogenesis [4].
• Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke's pouch and increases cell apoptosis during mouse pituitary development [5].
• To gain insights into the mechanism of Lhx3 function in pituitary development, we further analyzed the Lhx3 deficient mutants by examination of early pituitary marker expression, cell proliferation, and cell apoptosis [5].
• Our results thus underscore the view that Lhx3 functions downstream of the Pitx factors in the same transcriptional cascade that controls growth and early cell differentiation of the developing pituitary gland [5].

Anatomical context of Lhx3

• Conversely, the misexpression of Lhx3 in dorsal-exiting motor neurons is sufficient to reorient their axonal projections ventrally [2].
• We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells [6].
• These data suggest a potential role for mLIM-3 in the transcriptional regulation of certain genes during morphogenesis and/or maintenance of the differentiated state of the pituitary, motor neurons, and pineal gland [7].

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

• Linkage mapping of the gene for the LIM-homeoprotein LIM3 (locus Lhx3) to mouse chromosome 2 [13].
• Ontogeny studies using in situ hybridization demonstrated that mLIM-3 transcripts can be detected on embryonic day 11 (e11) in the primordium of the hypophysis [7].

References