The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Hand2  -  heart and neural crest derivatives...

Mus musculus

Synonyms: AI225906, AI661148, Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2, Dhand, Ehand2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Hand2


Psychiatry related information on Hand2

  • T helper cell differentiation into Th2 effector cell may be a major contributing factor to impaired cellular immunity following chronic drug abuse [6].
  • We have investigated the anti-tumour activity of CD4+ BALB/c Th1 and Th2 clones which recognize a processed Id of the syngeneic lambda 2(315) L chain in the context of the class II MHC molecule I-Ed [7].

High impact information on Hand2

  • In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12 [8].
  • It appears, however, that after immunization, the antigen-specific response is predominantly polarized toward a Th2-type response, with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines [9].
  • Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response [10].
  • Dimerization partner choice by Twist1 and Hand2 can be modulated by protein kinase A- and protein phosphatase 2A-regulated phosphorylation of conserved helix I residues [1].
  • Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJkappa [11].

Chemical compound and disease context of Hand2


Biological context of Hand2

  • RV hypoplasia was associated with downregulation of Hand2, a transcription factor previously shown to regulate formation of the RV [17].
  • These structural changes are preceded by aberrant expansion of proximal first arch gene expression into the distal arch, in addition to the previously described loss of a Dlx6/Hand2 expression network [18].
  • In some transgenic embryos with heterogeneous expression of the transgene, a muscular septum did not form in a region where Hand2 was expressed, but an incomplete septum was identifiable in a region where Hand2 was not expressed, suggesting that septum formation was strictly regulated by the expression domain of Hand2 [19].
  • dHAND/Hand2 is a basic helix-loop-helix transcription factor required for the development of the heart, pharyngeal arches, and vasculature and is expressed during embryogenesis [20].
  • Our description of the cardiac phenotype of dHAND mutant embryos is the first demonstration of a single gene controlling the formation of the mesodermally derived right ventricle and the neural crest-derived aortic arches and reveals a novel cardiogenic subprogramme for right ventricular development [21].

Anatomical context of Hand2


Associations of Hand2 with chemical compounds


Physical interactions of Hand2


Regulatory relationships of Hand2

  • The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development [29].
  • METHODS: Therefore, we established interleukin (IL)-4 transgenic mice under the control of a cardiac alpha-myosin heavy chain promotor and transplanted IL-4-expressing heart allografts into unmodified recipients to determine the actual contribution of the Th2 bias to allograft acceptance [30].
  • The results also suggest that Th1 responses may be more preferentially suppressed by the SINOMENIUM ACUTUM-derived alkaloid compared to Th2 responses [31].
  • These results suggest that Akt-mediated signaling may regulate dHAND transcriptional activity through the modulation of its DNA binding activity during embryogenesis [32].
  • We propose that Hand 2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash 1 [33].

Other interactions of Hand2

  • dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors that are expressed in mesodermal and neural crest-derived structures of the developing heart [21].
  • Normal expression of Hand2, a transcription factor essential for right ventricular development, in cardiomyocyte precursors is dependent upon m-Bop [34].
  • The bHLH transcription factor dHAND is required for establishment of SHH signaling by the limb bud organizer in posterior mesenchyme, a step crucial to development of vertebrate paired appendages [35].
  • Furthermore, genetic interaction of GLI3 and dHAND directs establishment of the SHH/FGF signaling feedback loop by restricting the BMP antagonist GREMLIN posteriorly [35].
  • Now, Firulli et al.1 show in mouse and chick that ectopic expression of a related bHLH protein, Hand2, results in phenocopies of the limb defects caused by Twist1 loss-of-function mutations [36].

Analytical, diagnostic and therapeutic context of Hand2

  • These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation [37].
  • We show using yeast and mammalian two-hybrid assays as well as biochemical pull-down assays that eHAND and dHAND are capable of forming both HAND homo- and heterodimers in vivo [38].
  • However, the differential activation of Th2 cells may be simply the result of allograft acceptance/tolerance induction instead of a contribution to the maintenance of grafts [30].
  • Oral administration of TBT, which most effectively promoted Th2 polarization in vitro, exacerbated airway inflammation in a murine model of allergic asthma with concomitant enhancement of Th2-type immunity [25].
  • Signal Transducer and Activator of Transcription (STAT)4 and STAT6 are key proteins involved in the CD4(+) T cell differentiation pathways leading to T helper type (Th)1 and Th2 cell development, respectively [39].


  1. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Firulli, B.A., Krawchuk, D., Centonze, V.E., Vargesson, N., Virshup, D.M., Conway, S.J., Cserjesi, P., Laufer, E., Firulli, A.B. Nat. Genet. (2005) [Pubmed]
  2. Neonatal peptide exposure can prime T cells and, upon subsequent immunization, induce their immune deviation: implications for antibody vs. T cell-mediated autoimmunity. Singh, R.R., Hahn, B.H., Sercarz, E.E. J. Exp. Med. (1996) [Pubmed]
  3. Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites. Finkelman, F.D., Madden, K.B., Cheever, A.W., Katona, I.M., Morris, S.C., Gately, M.K., Hubbard, B.R., Gause, W.C., Urban, J.F. J. Exp. Med. (1994) [Pubmed]
  4. Targeted deletion of a branchial arch-specific enhancer reveals a role of dHAND in craniofacial development. Yanagisawa, H., Clouthier, D.E., Richardson, J.A., Charité, J., Olson, E.N. Development (2003) [Pubmed]
  5. Improved Outcomes in NOD Mice Treated with a Novel Th2 Cytokine-Biasing NKT Cell Activator. Forestier, C., Takaki, T., Molano, A., Im, J.S., Baine, I., Jerud, E.S., Illarionov, P., Ndonye, R., Howell, A.R., Santamaria, P., Besra, G.S., Dilorenzo, T.P., Porcelli, S.A. J. Immunol. (2007) [Pubmed]
  6. Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet. Roy, S., Wang, J., Gupta, S., Charboneau, R., Loh, H.H., Barke, R.A. J. Neuroimmunol. (2004) [Pubmed]
  7. Anti-tumour activity of idiotype-specific, MHC-restricted Th1 and Th2 clones in vitro and in vivo. Lauritzsen, G.F., Weiss, S., Bogen, B. Scand. J. Immunol. (1993) [Pubmed]
  8. Interleukin-18 regulates both Th1 and Th2 responses. Nakanishi, K., Yoshimoto, T., Tsutsui, H., Okamura, H. Annu. Rev. Immunol. (2001) [Pubmed]
  9. The design of vaccines against Helicobacter pylori and their development. Del Giudice, G., Covacci, A., Telford, J.L., Montecucco, C., Rappuoli, R. Annu. Rev. Immunol. (2001) [Pubmed]
  10. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Weiner, H.L., Friedman, A., Miller, A., Khoury, S.J., al-Sabbagh, A., Santos, L., Sayegh, M., Nussenblatt, R.B., Trentham, D.E., Hafler, D.A. Annu. Rev. Immunol. (1994) [Pubmed]
  11. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Amsen, D., Blander, J.M., Lee, G.R., Tanigaki, K., Honjo, T., Flavell, R.A. Cell (2004) [Pubmed]
  12. Dietary arginine enhances adhesion molecule and T helper 2 cytokine expression in mice with gut-derived sepsis. Yeh, C.L., Hsu, C.S., Chiu, W.C., Hou, Y.C., Yeh, S.L. Shock (2006) [Pubmed]
  13. Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic-pituitary-adrenal axis activation in mice. Viveros-Paredes, J.M., Puebla-Pérez, A.M., Gutiérrez-Coronado, O., Sandoval-Ramírez, L., Villaseñor-García, M.M. Int. Immunopharmacol. (2006) [Pubmed]
  14. Overexpression of CIITA in T Cells Aggravates Th2-Mediated Colitis in Mice. Kim, T.W., Park, H.J., Choi, E.Y., Jung, K.C. J. Korean Med. Sci. (2006) [Pubmed]
  15. The biology of chemokines and their receptors. Rossi, D., Zlotnik, A. Annu. Rev. Immunol. (2000) [Pubmed]
  16. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Youssef, S., Stüve, O., Patarroyo, J.C., Ruiz, P.J., Radosevich, J.L., Hur, E.M., Bravo, M., Mitchell, D.J., Sobel, R.A., Steinman, L., Zamvil, S.S. Nature (2002) [Pubmed]
  17. Morphogenesis of the right ventricle requires myocardial expression of Gata4. Zeisberg, E.M., Ma, Q., Juraszek, A.L., Moses, K., Schwartz, R.J., Izumo, S., Pu, W.T. J. Clin. Invest. (2005) [Pubmed]
  18. Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity. Ruest, L.B., Xiang, X., Lim, K.C., Levi, G., Clouthier, D.E. Development (2004) [Pubmed]
  19. Essential role of Hand2 in interventricular septum formation and trabeculation during cardiac development. Togi, K., Yoshida, Y., Matsumae, H., Nakashima, Y., Kita, T., Tanaka, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  20. Tooth-type specific expression of dHAND/Hand2: possible involvement in murine lower incisor morphogenesis. Abe, M., Tamamura, Y., Yamagishi, H., Maeda, T., Kato, J., Tabata, M.J., Srivastava, D., Wakisaka, S., Kurisu, K. Cell Tissue Res. (2002) [Pubmed]
  21. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Srivastava, D., Thomas, T., Lin, Q., Kirby, M.L., Brown, D., Olson, E.N. Nat. Genet. (1997) [Pubmed]
  22. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Firulli, A.B., McFadden, D.G., Lin, Q., Srivastava, D., Olson, E.N. Nat. Genet. (1998) [Pubmed]
  23. The basic helix-loop-helix transcription factor, dHAND, is required for vascular development. Yamagishi, H., Olson, E.N., Srivastava, D. J. Clin. Invest. (2000) [Pubmed]
  24. Extra-embryonic vasculature development is regulated by the transcription factor HAND1. Morikawa, Y., Cserjesi, P. Development (2004) [Pubmed]
  25. Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation. Kato, T., Tada-Oikawa, S., Takahashi, K., Saito, K., Wang, L., Nishio, A., Hakamada-Taguchi, R., Kawanishi, S., Kuribayashi, K. Eur. J. Immunol. (2006) [Pubmed]
  26. The progesterone derivative dydrogesterone down-regulates neurokinin 1 receptor expression on lymphocytes, induces a Th2 skew and exerts hypoalgesic effects in mice. Orsal, A.S., Blois, S., Labuz, D., Peters, E.M., Schaefer, M., Arck, P.C. J. Mol. Med. (2006) [Pubmed]
  27. How the MHC selects Th1/Th2 immunity. Murray, J.S. Immunol. Today (1998) [Pubmed]
  28. Differential expression of alpha3 fucosyltransferases in Th1 and Th2 cells correlates with their ability to bind P-selectin. van Wely, C.A., Blanchard, A.D., Britten, C.J. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  29. The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development. Charité, J., McFadden, D.G., Olson, E.N. Development (2000) [Pubmed]
  30. Murine interleukin 4 transgenic heart allograft survival prolonged with down-regulation of the Th1 cytokine mRNA in grafts. Takeuchi, T., Ueki, T., Sunaga, S., Ikuta, K., Sasaki, Y., Li, B., Moriyama, N., Miyazaki, J., Kawabe, K. Transplantation (1997) [Pubmed]
  31. Suppression of Th1 and Th2 Immune Responses in Mice by Sinomenine, an Alkaloid Extracted from the Chinese Medicinal Plant Sinomenium acutum. Feng, H., Yamaki, K., Takano, H., Inoue, K., Yanagisawa, R., Yoshino, S. Planta Med. (2006) [Pubmed]
  32. Akt-dependent phosphorylation negatively regulates the transcriptional activity of dHAND by inhibiting the DNA binding activity. Murakami, M., Kataoka, K., Fukuhara, S., Nakagawa, O., Kurihara, H. Eur. J. Biochem. (2004) [Pubmed]
  33. The basic helix-loop-helix factor Hand 2 regulates autonomic nervous system development. Morikawa, Y., Dai, Y.S., Hao, J., Bonin, C., Hwang, S., Cserjesi, P. Dev. Dyn. (2005) [Pubmed]
  34. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Gottlieb, P.D., Pierce, S.A., Sims, R.J., Yamagishi, H., Weihe, E.K., Harriss, J.V., Maika, S.D., Kuziel, W.A., King, H.L., Olson, E.N., Nakagawa, O., Srivastava, D. Nat. Genet. (2002) [Pubmed]
  35. Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling. te Welscher, P., Fernandez-Teran, M., Ros, M.A., Zeller, R. Genes Dev. (2002) [Pubmed]
  36. A twisted hand: bHLH protein phosphorylation and dimerization regulate limb development. Cai, J., Jabs, E.W. Bioessays (2005) [Pubmed]
  37. Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis. Inoue, J., Aramaki, Y. J. Immunol. (2007) [Pubmed]
  38. The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function. Firulli, B.A., Hadzic, D.B., McDaid, J.R., Firulli, A.B. J. Biol. Chem. (2000) [Pubmed]
  39. Immune-mediated neuroprotection of axotomized mouse facial motoneurons is dependent on the IL-4/STAT6 signaling pathway in CD4(+) T cells. Deboy, C.A., Xin, J., Byram, S.C., Serpe, C.J., Sanders, V.M., Jones, K.J. Exp. Neurol. (2006) [Pubmed]
WikiGenes - Universities