Hlx belongs to the class of homeobox transcription factors, initially cloned from a B-lymphocyte cell line.[8] Targeted knockout of the gene has demonstrated its vital role in liver and gut organogenesis.[9] Its expression is first noticed in embryonic day 9.5 (E9.5) in thesplanchnic mesoderm caudal to the level of the heart and foregut pocket, and in the branchial arches. Around E10- E12.5, the expression becomes more prominent in themesenchyme of the visceral organs of the gut such as liver, intestines and gall bladder.[10] Hlx is essential for liver and gut expansion, but not for onset of their development. Heterozygous knockouts of Hlx (Hlx+/−) are normal whereas homozygous knockouts (Hlx−/–) develop severe hypoplasia of the liver and gut along with anaemia. Hlx controls the epithelial-mesenchymal interaction necessary for liver and gut expansion.[9] At E8.0, the primary liver bud is formed from the midgutendoderm in response to signals from thecardiogenic mesoderm. This is followed by signals from theseptum transversum that induce epithelial-mesenchymal transition in the hepatic progenitors of the gut endoderm.[11][12] In a third stage, these signaling factors induce the liver endoderm to undergo proliferation and form liver cords. The same factor controls gut proliferation, and Hlx governs its expression. Although these mice develop anaemia, it is likely due to insufficient support from the liver in producing matrix component needed for hematopoiesis rather than an intrinsic defect in the hematopoietic cells.[9]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Deguchi Y, Moroney JF, Wilson GL, Fox CH, Winter HS, Kehrl JH (April 1991). "Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes".The New Biologist.3 (4):353–63.PMID1676597.
^Kennedy MA, Rayner JC, Morris CM (July 1994). "Genomic structure, promoter sequence, and revised translation of human homeobox gene HLX1".Genomics.22 (2):348–55.doi:10.1006/geno.1994.1394.PMID7806220.
^Fukuda-Taira S (1981). "Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm".Journal of Embryology and Experimental Morphology.63:111–25.PMID7310284.
Deguchi Y, Yamanaka Y, Theodossiou C, Najfeld V, Kehrl JH (March 1993). "High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity".Leukemia.7 (3):446–51.PMID7680402.
Nishimura DY, Purchio AF, Murray JC (February 1993). "Linkage localization of TGFB2 and the human homeobox gene HLX1 to chromosome 1q".Genomics.15 (2):357–64.doi:10.1006/geno.1993.1068.PMID8095486.
Quinn LM, Johnson BV, Nicholl J,Sutherland GR, Kalionis B (March 1997). "Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal-less family, DLX4".Gene.187 (1):55–61.doi:10.1016/S0378-1119(96)00706-8.PMID9073066.
