Disease relevance of Hlx1

• Later infection with Hlx-expressing retrovirus showed no effect [1].

High impact information on Hlx1

• The divergent murine homeo box gene Hlx is expressed in restricted hematopoietic cell types and, during embryogenesis, prominently in visceral mesenchyme of the developing liver, gall bladder, and gut [2].
• Hlx is normally expressed in visceral mesenchyme lying adjacent to the developing liver and gut epithelia affected by the mutation, but not in the epithelia themselves [2].
• Moreover, because mutation of Hlx blocked liver growth but not its specification, early morphogenesis, or differentiation, development of this organ appears to occur by step-wise inductive interactions under separate genetic control [2].
• Hence, Hlx regulates a mesenchymal-epithelial interaction that drives a vital growth phase in visceral organogenesis [2].
• RNA analysis of 67 murine hematopoietic cell lines and normal hematopoietic cells revealed Hlx expression throughout the myeloid/macrophage lineage and at early stages of B lymphocyte development but not in T lymphocytes, erythroid cells, or mast cells [3].

Biological context of Hlx1

• We describe here a new murine homeo box gene, denoted Hlx, which is expressed within specific hematopoietic lineages [3].
• The cDNA sequence indicates that Hlx differs markedly from known vertebrate homeo box genes, and linkage analysis of an interspecific murine backcross showed that it resides at a novel homeo box locus on the distal portion of mouse chromosome 1 [3].
• Here we report further characterization of the mouse Hlx gene, including an additional 3.7 kb of 5' sequence as well as the sequence of the three introns [4].
• A number of consensus transcription factor binding sites were conserved between the mouse and human Hlx genes both within and outside of the highly conserved regions [4].
• Mice constitutively expressing an Hlx transgene driven by a CD4 promoter showed marked reduction in the CD4+CD8+ thymocyte population [1].

Anatomical context of Hlx1

• It probably also functions outside the hematopoietic system, however, because Hlx mRNA could be detected in diverse adult tissues and in embryos from as early as day 8 of development [3].
• To address its biologic action more directly, Hlx expression vectors were introduced into seven mouse hematopoietic cell lines representing several lineages [5].
• Enforced expression of Hlx homeobox gene prompts myeloid cell maturation and altered adherence properties of T cells [5].
• In the anterior-posterior aspect of the developing sclerotome, Hlx expression was out of register with original segmental boundaries (intersomitic fissures), a pattern consistent with a classical hypothesis that the developing vertebral column undergoes resegmentation [6].
• Hlx expression was also observed in vibrissae, pericardium, snout mesenchyme, and meningeal epithelium [6].

Other interactions of Hlx1

• Overexpression of Hlx in FDC-P1 cells downregulated two markers of myeloid immaturity, Thy-1 and CD34, and also promoted changes in cellular and colony morphology, indicative of limited differentiation [5].

Analytical, diagnostic and therapeutic context of Hlx1

• We have determined the expression pattern of the divergent homeobox gene Hlx during post-implantation mouse development, utilizing in situ hybridization [6].

References