Disease relevance of Tlx1

• Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively [1].
• These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis [2].
• As Hoxll can function as a transcription factor, we examined the spatial and temporal mRNA expression patterns of Hox11 and a candidate target gene, the Wilm's tumor gene Wt1, in the developing spleen [3].

High impact information on Tlx1

• To assess the functional role of the orphan homeobox gene Hox11, we have generated Hox11-deficient mice through gene targeting [4].
• Hox11 is normally expressed in the splenic anlage arising from the splanchnic mesoderm [4].
• Hox11 controls the genesis of a single organ, providing new insight into the genetic regulation of morphogenesis [4].
• Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1 [5].
• Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral [5].

Biological context of Tlx1

• Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord [6].
• Using a fluorescence in situ hybridization assay and interspecific backcross panel mapping, we have localized the Cig30 locus to the distal region of mouse chromosome 19, between the Tlx1 and Ins1 loci [7].
• The homeobox genes Hox11 and Bapx1, shown previously to be essential regulators of spleen organogenesis, and a lacZ reporter introduced into the capsulin locus, were expressed in the early splenic primordium, derived from the splanchnic mesoderm, of homozygous mutant embryos [8].
• The proposed gene orders and genetic distances for Tlx-1 and Tlx-2 are centromere 19-Lpc-1-(25.53 cM)-Pltr-4-(5.32 cM)-Tlx-1- (3.19 cM)-Ins-1-(7.45 cM)-Xmv-18, and centromere 6-Tcrb-(12.90 cM)-Mltr-3-(10.75 cM)-Tlx-2-(18.42 cM)-Xmv-6 [9].
• Study of Aldh1 gene expression during spleen development showed that the presence of Aldh1 mRNA inversely correlated with Hox11 [10].

Anatomical context of Tlx1

• Tbx1 is also required for normal expression of Tlx1 and Fgf10 in pharyngeal mesoderm, in addition to correct neural crest cell patterning in the mandibular arch [11].
• Pbx1 and Hox11 genetically interact in spleen formation and loss of either is associated with a similar reduction of progenitor cell proliferation and failed expansion of the splenic anlage [12].
• Neither Hox11L1 nor Hox11L2 was expressed in the branchial arches or their motor nuclei within wild-type or Hox11-/- mice [13].
• Additionally, Hox11 is expressed in the surface ectoderm of the first branchial arch in the region destined to become the tongue and teeth and then in ganglia innervating this area [13].
• In Hox11-/-<-->+/+ chimaeras, spleens were devoid of Hox11(-/-) cells, indicating that the genetic defect is cell autonomous and not due to failure of the organ anlage to attract and retain haematopoietic cells [14].

Other interactions of Tlx1

• Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates [6].
• These studies establish a Pbx1-Hox11-dependent genetic and transcriptional pathway in spleen ontogeny [12].
• As described in this study, removal of the last Hox11 paralogous member, Hoxc11, results in the complete loss of metanephric kidney induction [15].
• On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice [16].
• Hox11 is required to maintain normal Wt1 mRNA levels in the developing spleen [3].

Analytical, diagnostic and therapeutic context of Tlx1

• In order to elucidate the role, we examined the expression of Hox11 in normal lymphocytes by a reverse transcriptase-polymerase chain reaction analysis [17].
• Comparative promoter and homeodomain sequence analyses suggest that it is related to the Hox11 gene, which belongs to the Tlx homeobox family [18].

References