Hoxa9

Summary

Gene Symbol: Hoxa9
Description: homeobox A9
Alias: D6a9, Hox-1.7, homeobox protein Hox-A9, homeo box A9, homeobox protein Hox-1.7
Species: mouse
Products:     Hoxa9

Top Publications

  1. Gaunt S, Dean W, Sang H, Burton R. Evidence that Hoxa expression domains are evolutionarily transposed in spinal ganglia, and are established by forward spreading in paraxial mesoderm. Mech Dev. 1999;82:109-18 pubmed
    ..We discuss this as evidence that Hox expression in paraxial mesoderm spreads forward, as earlier found for neurectoderm and lateral plate mesoderm, in a process that occurs independently of cell movement. ..
  2. LaRonde LeBlanc N, Wolberger C. Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. Genes Dev. 2003;17:2060-72 pubmed
    ..We report here the 1.9-A-resolution structure of a posterior HOX protein, HoxA9, complexed with Pbx1 and DNA, which reveals that the posterior Hox hexapeptide adopts an altered conformation as ..
  3. Nakamura T, Largaespada D, Shaughnessy J, Jenkins N, Copeland N. Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias. Nat Genet. 1996;12:149-53 pubmed
    ..we identify three genes whose expression is activated by proviral integration in BXH-2 leukaemias; Hoxa7, Hoxa9, and a Pbx1-related homeobox gene, Meis1...
  4. Fromental Ramain C, Warot X, Lakkaraju S, Favier B, Haack H, Birling C, et al. Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning. Development. 1996;122:461-72 pubmed
  5. Lawrence H, Helgason C, Sauvageau G, Fong S, Izon D, Humphries R, et al. Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Blood. 1997;89:1922-30 pubmed
    ..The HOXA9 gene is expressed in CD34+ marrow cells and in developing lymphocytes...
  6. Gwin K, Frank E, Bossou A, Medina K. Hoxa9 regulates Flt3 in lymphohematopoietic progenitors. J Immunol. 2010;185:6572-83 pubmed publisher
    ..In this study, we show downregulation of a developmentally regulated cluster of hoxa genes, notably hoxa9, coincides with induction of EBF at the Pro-B cell stage of B cell differentiation...
  7. Moens C, Selleri L. Hox cofactors in vertebrate development. Dev Biol. 2006;291:193-206 pubmed
  8. Shen W, Rozenfeld S, Kwong A, Köm ves L, Lawrence H, Largman C. HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Mol Cell Biol. 1999;19:3051-61 pubmed
    ..MEIS, and PBX homeodomain protein families is associated with leukemias, and retrovirally driven coexpression of HOXA9 and MEIS1 is sufficient to induce myeloid leukemia in mice...
  9. Hu Y, Fong S, Ferrell C, Largman C, Shen W. HOXA9 modulates its oncogenic partner Meis1 to influence normal hematopoiesis. Mol Cell Biol. 2009;29:5181-92 pubmed publisher
    While investigating the mechanism of action of the HOXA9 protein, we serendipitously identified Meis1 as a HOXA9 regulatory target...

More Information

Publications62

  1. Kumar A, Hudson W, Chen W, Nishiuchi R, Yao Q, Kersey J. Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood. 2004;103:1823-8 pubmed
    ..Numerous studies have implicated HOXA9 as one of the possible targets of MLL fusion proteins...
  2. Zeisig B, Milne T, Garcia Cuellar M, Schreiner S, Martin M, Fuchs U, et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol. 2004;24:617-28 pubmed
    ..Microarray analysis performed on these conditionally transformed cells revealed Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets upregulated by MLL-ENL-ERtm...
  3. Hu Y, Passegue E, Fong S, Largman C, Lawrence H. Evidence that the Pim1 kinase gene is a direct target of HOXA9. Blood. 2007;109:4732-8 pubmed
    The HOXA9 homeoprotein exerts dramatic effects in hematopoiesis. Enforced expression of HOXA9 enhances proliferation of primitive blood cells, expands hematopoietic stem cells (HSCs), and leads to myeloid leukemia...
  4. So C, Karsunky H, Wong P, Weissman I, Cleary M. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood. 2004;103:3192-9 pubmed
    ..with normal hematopoiesis, whereas inappropriate maintenance of Hox gene expression, particularly Hoxa7 and Hoxa9, is a feature of leukemias harboring mixed-lineage leukemia (MLL) mutations...
  5. Faber J, Krivtsov A, Stubbs M, Wright R, Davis T, van den Heuvel Eibrink M, et al. HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood. 2009;113:2375-85 pubmed publisher
    ..profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes, including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias using RNA ..
  6. Chen F, Capecchi M. Paralogous mouse Hox genes, Hoxa9, Hoxb9, and Hoxd9, function together to control development of the mammary gland in response to pregnancy. Proc Natl Acad Sci U S A. 1999;96:541-6 pubmed
    ..Analysis of mice with mutant Hoxa9, Hoxb9, and Hoxd9 genes shows that these paralogous genes are required for mediating the expansion and/or ..
  7. Izon D, Rozenfeld S, Fong S, Komuves L, Largman C, Lawrence H. Loss of function of the homeobox gene Hoxa-9 perturbs early T-cell development and induces apoptosis in primitive thymocytes. Blood. 1998;92:383-93 pubmed
    ..Hoxa-9 appears to play a previously unsuspected role in T-cell ontogeny by modulating cell survival of early thymocytes and by regulating their subsequent differentiation. ..
  8. Shen W, Montgomery J, Rozenfeld S, Moskow J, Lawrence H, Buchberg A, et al. AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol. 1997;17:6448-58 pubmed
    ..DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets. ..
  9. Bernstein B, Kamal M, Lindblad Toh K, Bekiranov S, Bailey D, Huebert D, et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell. 2005;120:169-81 pubmed
    ..This suggests that the DNA elements that direct the methylation represent only a small fraction of the region or lie at some distance from the site. ..
  10. Lawrence H, Christensen J, Fong S, Hu Y, Weissman I, Sauvageau G, et al. Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells. Blood. 2005;106:3988-94 pubmed
    ..Hoxa-9 appears to be specifically required for normal hematopoietic stem cell function both in vitro and in vivo. ..
  11. Chen F, Capecchi M. Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions. Dev Biol. 1997;181:186-96 pubmed
    ..In particular, the sternum defects are greatly exacerbated. Interestingly, the defects in hoxb-9 and hoxa-9/ hoxb-9 mutant mice are concentrated along the axial column at points of transition between vertebral types. ..
  12. Fujino T, Yamazaki Y, Largaespada D, Jenkins N, Copeland N, Hirokawa K, et al. Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes. Exp Hematol. 2001;29:856-63 pubmed
    ..Cooperative activation between Hoxa9 and Meis1 is induced by retroviral integration in BXH2 murine myeloid leukemias and the myeloid leukemia cell line ..
  13. Calvo K, Sykes D, Pasillas M, Kamps M. Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of Hoxa9, Hoxa7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of Hoxa9 and Meis1. Oncogene. 2002;21:4247-56 pubmed
    The association between acute myeloid leukaemia (AML) and the aberrant expression of Hoxa9 is evidenced by (1) proviral activation of Hoxa9 and Meis1 in BXH-2 murine AML, (2) formation of the chimeric Nup98-HoxA9 transactivator protein ..
  14. Mamo A, Krosl J, Kroon E, Bijl J, Thompson A, Mayotte N, et al. Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation. Blood. 2006;108:622-9 pubmed
    The Hoxa9 and Meis1 genes represent important oncogenic collaborators activated in a significant proportion of human leukemias with genetic alterations in the MLL gene...
  15. Garcia Cuellar M, Steger J, Füller E, Hetzner K, Slany R. Pbx3 and Meis1 cooperate through multiple mechanisms to support Hox-induced murine leukemia. Haematologica. 2015;100:905-13 pubmed publisher
    ..abrogated the ability to enhance proliferation and colony-forming cell numbers in primary cells transformed by Hoxa9. Furthermore, expression of Meis1 target genes Flt3 and Trib2 was dependent on Pbx3/Meis1 dimerization...
  16. Kong C, Sham M, So C, Cheah K, Chen S, Chan L. The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice. Leukemia. 2006;20:1829-39 pubmed
    ..We believe studies of MLL fusion proteins in ES cells combined with in vivo animal models offer new approaches to the dissection of molecular events in multistep pathogenesis of leukaemia. ..
  17. McIntyre D, Rakshit S, Yallowitz A, Loken L, Jeannotte L, Capecchi M, et al. Hox patterning of the vertebrate rib cage. Development. 2007;134:2981-9 pubmed
    ..Thus, the ;Hox code' in somitic mesoderm is the result of the distinct, graded effects of two or more Hox paralogous groups functioning in any anteroposterior location. ..
  18. Woltering J, Duboule D. Tetrapod axial evolution and developmental constraints; Empirical underpinning by a mouse model. Mech Dev. 2015;138 Pt 2:64-72 pubmed publisher
  19. Scotti M, Kmita M. Recruitment of 5' Hoxa genes in the allantois is essential for proper extra-embryonic function in placental mammals. Development. 2012;139:731-9 pubmed publisher
    ..Finally, using a series of targeted recombination and transgenic assays, we provide evidence that the regulatory mechanism underlying Hoxa expression in the allantois is extremely complex and relies on several cis-regulatory sequences...
  20. Raines A, Adam M, Magella B, Meyer S, Grimes H, Dey S, et al. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development. 2013;140:2942-52 pubmed publisher
    ..the use of a novel recombineering strategy to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10 and Hoxa11 genes, as well as their paralogs on the HoxD cluster...
  21. Jurberg A, Aires R, Varela Lasheras I, Novoa A, Mallo M. Switching axial progenitors from producing trunk to tail tissues in vertebrate embryos. Dev Cell. 2013;25:451-62 pubmed publisher
    ..Our findings provide a perspective to understand the evolution of the vertebrate body plan...
  22. Fujimoto S, Araki K, Chisaka O, Araki M, Takagi K, Yamamura K. Analysis of the murine Hoxa-9 cDNA: an alternatively spliced transcript encodes a truncated protein lacking the homeodomain. Gene. 1998;209:77-85 pubmed
    ..5kb transcript in the same tissues, indicating that 1.9kb transcript corresponds to Hoxa-9T mRNA. We have also determined the transcriptional start site of Hoxa-9T. ..
  23. Takihara Y, Tomotsune D, Shirai M, Katoh Fukui Y, Nishii K, Motaleb M, et al. Targeted disruption of the mouse homologue of the Drosophila polyhomeotic gene leads to altered anteroposterior patterning and neural crest defects. Development. 1997;124:3673-82 pubmed
    ..These results indicate that the rae28 gene is involved in the regulation of Hox gene expression and segment specification during paraxial mesoderm and neural crest development. ..
  24. Taylor M, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, et al. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell. 2005;8:323-35 pubmed
  25. Ko S, Ladanyi A, Lengyel E, Naora H. Expression of the homeobox gene HOXA9 in ovarian cancer induces peritoneal macrophages to acquire an M2 tumor-promoting phenotype. Am J Pathol. 2014;184:271-81 pubmed publisher
    ..p. xenograft models of ovarian cancer that expressed HOXA9, a homeobox gene that is associated with poor prognosis in patients with ovarian cancer...
  26. Dash A, Williams I, Kutok J, Tomasson M, Anastasiadou E, Lindahl K, et al. A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proc Natl Acad Sci U S A. 2002;99:7622-7 pubmed
    ..with acquisition of secondary chromosomal translocations, including the t(7;11)(p15;p15) resulting in the NUP98/HOXA9 fusion protein. We demonstrate that BCR/ABL cooperates with NUP98/HOXA9 to cause blast crisis in a murine model...
  27. Sheikh B, Downer N, Phipson B, Vanyai H, Kueh A, McCarthy D, et al. MOZ and BMI1 play opposing roles during Hox gene activation in ES cells and in body segment identity specification in vivo. Proc Natl Acad Sci U S A. 2015;112:5437-42 pubmed publisher
    ..We propose that chromatin-modifying complexes have a previously unappreciated role during the initiation phase of Hox gene expression, which is critical for the correct specification of body segment identity. ..
  28. Chariot A, Gielen J, Merville M, Bours V. The homeodomain-containing proteins: an update on their interacting partners. Biochem Pharmacol. 1999;58:1851-7 pubmed
    ..We also outline the molecular programs that are regulated by the transcriptional complexes involving the HOX gene products and where new pharmacological tools could find interesting targets. ..
  29. Laurent A, Bihan R, Deschamps S, Guerrier D, Dupé V, Omilli F, et al. Identification of a new type of PBX1 partner that contains zinc finger motifs and inhibits the binding of HOXA9-PBX1 to DNA. Mech Dev. 2007;124:364-76 pubmed
    ..showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site...
  30. Gwin K, Shapiro M, Dolence J, Huang Z, Medina K. Hoxa9 and Flt3 signaling synergistically regulate an early checkpoint in lymphopoiesis. J Immunol. 2013;191:745-54 pubmed publisher
    b>Hoxa9 and Flt3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow...
  31. Burke A, Nelson C, Morgan B, Tabin C. Hox genes and the evolution of vertebrate axial morphology. Development. 1995;121:333-46 pubmed
    ..The recognition of mechanistic homology supports the historical homology of basic patterning mechanisms between all organisms that share these genes. ..
  32. Ford H. Homeobox genes: a link between development, cell cycle, and cancer?. Cell Biol Int. 1998;22:397-400 pubmed
  33. Oakley K, Han Y, Vishwakarma B, Chu S, Bhatia R, Gudmundsson K, et al. Setbp1 promotes the self-renewal of murine myeloid progenitors via activation of Hoxa9 and Hoxa10. Blood. 2012;119:6099-108 pubmed publisher
    ..Self-renewal after immortalization requires continuous Setbp1 expression. We also found that Hoxa9 and Hoxa10 mRNA are present at dramatically higher levels in Setbp1-immortalized cells compared with other ..
  34. Nakamura T, Jenkins N, Copeland N. Identification of a new family of Pbx-related homeobox genes. Oncogene. 1996;13:2235-42 pubmed
    The expression of Meis1 (a novel Pbx-related homeobox gene) and either Hoxa7 or Hoxa9 are coactivated by retroviral integration in BXH2 murine myeloid leukemias (T Nakamura, DA Largaespada, JD Shaughnessy Jr, NA Jenkins and NG Copeland (..
  35. McGrath K, Palis J. Expression of homeobox genes, including an insulin promoting factor, in the murine yolk sac at the time of hematopoietic initiation. Mol Reprod Dev. 1997;48:145-53 pubmed
    ..We hypothesize the early expression of insulin in the YS is required for the expansion of insulin responsive cells including primitive erythroblasts. ..
  36. Vijapurkar U, Fischbach N, Shen W, Brandts C, Stokoe D, Lawrence H, et al. Protein kinase C-mediated phosphorylation of the leukemia-associated HOXA9 protein impairs its DNA binding ability and induces myeloid differentiation. Mol Cell Biol. 2004;24:3827-37 pubmed
    b>HOXA9 expression is a common feature of acute myeloid leukemia, and high-level expression is correlated with poor prognosis...
  37. Benson G, Nguyen T, Maas R. The expression pattern of the murine Hoxa-10 gene and the sequence recognition of its homeodomain reveal specific properties of Abdominal B-like genes. Mol Cell Biol. 1995;15:1591-601 pubmed
    ..Thus, in vertebrates, structural similarities, coordinate transcriptional regulation, sites of expression, and binding site preferences all serve to distinguish AbdB from Antp Hox genes. ..
  38. Hu Y, Fong S, Largman C, Shen W. HOXA9 regulates miR-155 in hematopoietic cells. Nucleic Acids Res. 2010;38:5472-8 pubmed publisher
    b>HOXA9-mediated up-regulation of miR-155 was noted during an array-based analysis of microRNA expression in Hoxa9(-/-)bone marrow (BM) cells...
  39. Bijl J, Krosl J, Lebert Ghali C, Vacher J, Mayotte N, Sauvageau G. Evidence for Hox and E2A-PBX1 collaboration in mouse T-cell leukemia. Oncogene. 2008;27:6356-64 pubmed publisher
    ..in E2A-PBX1-induced lymphoid leukemia resulting in the overexpression of several Hoxa genes including Hoxa10, Hoxa9 and Hoxa7...
  40. Rijli F, Matyas R, Pellegrini M, Dierich A, Gruss P, Dolle P, et al. Cryptorchidism and homeotic transformations of spinal nerves and vertebrae in Hoxa-10 mutant mice. Proc Natl Acad Sci U S A. 1995;92:8185-9 pubmed
    ..These results reveal an important role of Hoxa-10 in patterning posterior body regions and suggest that Hox genes are involved in specifying regional identity of both segmented and nonovertly segmented structures of the developing body. ..
  41. Crawford Parks T, Ravel Chapuis A, Bondy Chorney E, Renaud J, Cote J, Jasmin B. Muscle-specific expression of the RNA-binding protein Staufen1 induces progressive skeletal muscle atrophy via regulation of phosphatase tensin homolog. Hum Mol Genet. 2017;26:1821-1838 pubmed publisher
    ..Collectively, our data demonstrate that Staufen1 is a novel atrophy-associated gene, and highlight its potential as a biomarker and therapeutic target for neuromuscular disorders and conditions. ..
  42. Ko S, Barengo N, Ladanyi A, Lee J, Marini F, Lengyel E, et al. HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts. J Clin Invest. 2012;122:3603-17 pubmed publisher
    ..In this study, we show that expression of HOXA9, a Müllerian-patterning gene, is strongly associated with poor outcomes in patients with EOC and in mouse ..
  43. Keeshan K, Shestova O, Ussin L, Pear W. Tribbles homolog 2 (Trib2) and HoxA9 cooperate to accelerate acute myelogenous leukemia. Blood Cells Mol Dis. 2008;40:119-21 pubmed
    ..Using Splinkerette PCR techniques, we identified proviral insertion near HoxA9 in a Trib2 monoclonal tumor, which resulted in greatly elevated HoxA9 expression...
  44. Staffas A, Arabanian L, Wei S, Jansson A, Ståhlman S, Johansson P, et al. Upregulation of Flt3 is a passive event in Hoxa9/Meis1-induced acute myeloid leukemia in mice. Oncogene. 2017;36:1516-1524 pubmed publisher
    b>HOXA9, MEIS1 and FLT3 are genes frequently upregulated in human acute myeloid leukemia...
  45. Fisher J, Peterson J, Reimer M, Stelloh C, Pulakanti K, Gerbec Z, et al. The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9. Leukemia. 2017;31:712-719 pubmed publisher
    ..of HSPCs in vitro through derepression of polycomb repressive complex 2 (PRC2) target genes, including Hoxa7 and Hoxa9. Importantly, knockdown of either Hoxa7 or Hoxa9 suppressed self-renewal, implying that both are critical ..
  46. Malek R, Gajula R, Williams R, Nghiem B, Simons B, Nugent K, et al. TWIST1-WDR5-Hottip Regulates Hoxa9 Chromatin to Facilitate Prostate Cancer Metastasis. Cancer Res. 2017;77:3181-3193 pubmed publisher
    ..During embryonic development, TWIST1 and HOXA9 are coexpressed in mouse prostate and then silenced postnatally...
  47. Collins C, Wang J, Miao H, Bronstein J, Nawer H, Xu T, et al. C/EBP? is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc Natl Acad Sci U S A. 2014;111:9899-904 pubmed publisher
    Homeobox A9 (HOXA9) is a homeodomain-containing transcription factor that plays a key role in hematopoietic stem cell expansion and is commonly deregulated in human acute leukemias...
  48. Hassawi M, Shestakova E, Fournier M, Lebert Ghali C, Vaisson G, Frison H, et al. Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression. Dev Dyn. 2014;243:145-58 pubmed publisher
    ..Here we studied whether Hoxa9 could enhance E2A-PBX1 leukemogenesis. We show that Hoxa9 confers a proliferative advantage to E2A-PBX1 B cells...
  49. Milne T, Kim J, Wang G, Stadler S, Basrur V, Whitcomb S, et al. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell. 2010;38:853-63 pubmed publisher
    MLL1 fusion proteins activate HoxA9 gene expression and cause aggressive leukemias that respond poorly to treatment, but how they recognize and stably bind to HoxA9 is not clearly understood...
  50. Novotny E, Compton S, Liu P, Collins F, Chandrasekharappa S. In vitro hematopoietic differentiation of mouse embryonic stem cells requires the tumor suppressor menin and is mediated by Hoxa9. Mech Dev. 2009;126:517-22 pubmed publisher
    ..MLL is also essential for hematopoiesis, and plays a critical role in leukemogenesis via epigenetic regulation of Hoxa9 expression that also requires menin. Therefore we chose to explore the role of menin in hematopoiesis...
  51. Yan J, Chen Y, Desmond A, Silva A, Yang Y, Wang H, et al. Cdx4 and menin co-regulate Hoxa9 expression in hematopoietic cells. PLoS ONE. 2006;1:e47 pubmed
    Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear...
  52. Katsumoto T, Aikawa Y, Iwama A, Ueda S, Ichikawa H, Ochiya T, et al. MOZ is essential for maintenance of hematopoietic stem cells. Genes Dev. 2006;20:1321-30 pubmed
    ..Analysis using microarray and flow cytometry revealed that expression of thrombopoietin receptor (c-Mpl), HoxA9, and c-Kit was down-regulated...
  53. Sheikh B, Downer N, Kueh A, Thomas T, Voss A. Excessive versus physiologically relevant levels of retinoic acid in embryonic stem cell differentiation. Stem Cells. 2014;32:1451-8 pubmed publisher
    ..Our results demonstrate that using RA at physiologically relevant levels to study the activation of Hox genes, more accurately reflects the molecular events during the early phase of Hox gene activation in vivo. ..