Gene Symbol: Hand2
Description: heart and neural crest derivatives expressed 2
Alias: heart- and neural crest derivatives-expressed protein 2, dHand protein, deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2, heart and neural crest derivatives expressed transcript 2
Species: rat
Products:     Hand2

Top Publications

  1. Thattaliyath B, Firulli B, Firulli A. The basic-helix-loop-helix transcription factor HAND2 directly regulates transcription of the atrial naturetic peptide gene. J Mol Cell Cardiol. 2002;34:1335-44 pubmed
    ..In efforts to identify downstream transcriptional targets, we have determined that HAND2 regulates the transcription of the Atrial Naturetic Peptide (ANP) gene...
  2. Srivastava D, Thomas T, Lin Q, Kirby M, Brown D, Olson E. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997;16:154-60 pubmed
  3. McFadden D, Charite J, Richardson J, Srivastava D, Firulli A, Olson E. A GATA-dependent right ventricular enhancer controls dHAND transcription in the developing heart. Development. 2000;127:5331-41 pubmed
    ..Since GATA factors are not chamber-restricted, these findings suggest the existence of positive and/or negative coregulators that cooperate with GATA factors to control right ventricular-specific gene expression in the developing heart. ..
  4. Thattaliyath B, Livi C, Steinhelper M, Toney G, Firulli A. HAND1 and HAND2 are expressed in the adult-rodent heart and are modulated during cardiac hypertrophy. Biochem Biophys Res Commun. 2002;297:870-5 pubmed
    ..Mouse expression of HAND1 and HAND2 was reported absent in the adult heart...
  5. Russell M, Kemp P, Wang L, Brody L, Izumo S. Molecular cloning of the human HAND2 gene. Biochim Biophys Acta. 1998;1443:393-9 pubmed
    We have cloned and characterized the coding sequence of the human HAND2 basic helix-loop-helix transcription factor. The amino acid sequence includes an amino-terminal polyalanine repeat which is precisely conserved in the rat HAND2 gene...
  6. Poizat C, Sartorelli V, Chung G, Kloner R, Kedes L. Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription. Mol Cell Biol. 2000;20:8643-54 pubmed
    ..These results provide evidence for a new mechanism of transcriptional repression caused by doxorubicin in which the selective degradation of p300 results in reduced p300-dependent transcription, including production of MEF2C mRNA. ..
  7. Bär H, Kreuzer J, Cojoc A, Jahn L. Upregulation of embryonic transcription factors in right ventricular hypertrophy. Basic Res Cardiol. 2003;98:285-94 pubmed
    ..Expression of GATA-4, Nkx-2.5/Csx, MEF-2 and dHAND protein was found to increase in the right ventricle after the banding procedure as determined by immunohistochemistry ..
  8. Morikawa Y, D Autréaux F, Gershon M, Cserjesi P. Hand2 determines the noradrenergic phenotype in the mouse sympathetic nervous system. Dev Biol. 2007;307:114-26 pubmed
    The basic helix-loop-helix (bHLH) transcription factor Hand2 has been shown to play a role in the development of the mammalian sympathetic nervous system (SNS); however, its precise role could not be uncovered because Hand2 is required ..
  9. D Autréaux F, Morikawa Y, Cserjesi P, Gershon M. Hand2 is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia. Development. 2007;134:2237-49 pubmed
    ..We now report that enteric Hand2 expression is limited to crest-derived cells, whereas Hand1 expression is restricted to muscle and interstitial ..

More Information


  1. Dai Y, Cserjesi P. The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer. J Biol Chem. 2002;277:12604-12 pubmed
    b>HAND2 (dHAND) is a basic helix-loop-helix (bHLH) transcription factor expressed in numerous tissues during development including the heart, limbs, and a subset of neural crest derivatives...
  2. Li W, Li Y. Regulation of dHAND protein expression by all-trans retinoic acid through ET-1/ETAR signaling in H9c2 cells. J Cell Biochem. 2006;99:478-84 pubmed
    ..The mechanism of ET-1/ETAR signaling in controlling the level of dHAND protein is to reduce the levels of dHAND mRNA...
  3. Yamagishi H, Yamagishi C, Nakagawa O, Harvey R, Olson E, Srivastava D. The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol. 2001;239:190-203 pubmed
    Nkx2.5/Csx and dHAND/Hand2 are conserved transcription factors that are coexpressed in the precardiac mesoderm and early heart tube and control distinct developmental events during cardiogenesis. To understand whether Nkx2...
  4. Rychlik J, Hsieh M, Eiden L, Lewis E. Phox2 and dHAND transcription factors select shared and unique target genes in the noradrenergic cell type. J Mol Neurosci. 2005;27:281-92 pubmed
    ..The Phox2 proteins were found to share all target genes, whereas dHAND binds to genes independently of Phox2a. ..
  5. Morikawa Y, Dai Y, Hao J, Bonin C, Hwang S, Cserjesi P. The basic helix-loop-helix factor Hand 2 regulates autonomic nervous system development. Dev Dyn. 2005;234:613-21 pubmed
    ..We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand 2 functions to promote ANS development as part of a larger transcriptional complex. ..
  6. Xiong W, He F, Morikawa Y, Yu X, Zhang Z, Lan Y, et al. Hand2 is required in the epithelium for palatogenesis in mice. Dev Biol. 2009;330:131-41 pubmed publisher
    The basic helix-loop-helix (bHLH) transcription factor Hand2 has been implicated in the development of multiple organs, including craniofacial organs...
  7. Zang M, Li Y, Xue L, Jia H, Jing H. Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C. J Cell Biochem. 2004;93:1255-66 pubmed
  8. Holler K, Hendershot T, Troy S, Vincentz J, Firulli A, Howard M. Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development. Dev Biol. 2010;341:291-304 pubmed publisher
    The basic helix-loop-helix DNA binding protein Hand2 has critical functions in cardiac development both in neural crest-derived and mesoderm-derived structures...
  9. Pellegrino M, Parrish D, Zigmond R, Habecker B. Cytokines inhibit norepinephrine transporter expression by decreasing Hand2. Mol Cell Neurosci. 2011;46:671-80 pubmed publisher
    ..b>Hand2 and Gata3 are transcription factors that induce noradrenergic genes during development and are present in mature ..
  10. Dirkx E, Gladka M, Philippen L, Armand A, Kinet V, Leptidis S, et al. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol. 2013;15:1282-93 pubmed publisher
    ..expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium...
  11. Zang M, Li Y, Wang H, Wang J, Jia H. Cooperative interaction between the basic helix-loop-helix transcription factor dHAND and myocyte enhancer factor 2C regulates myocardial gene expression. J Biol Chem. 2004;279:54258-63 pubmed
  12. Murakami M, Kataoka K, Tominaga J, Nakagawa O, Kurihara H. Differential cooperation between dHAND and three different E-proteins. Biochem Biophys Res Commun. 2004;323:168-74 pubmed
    ..By contrast, little signal was detected in the heart, suggesting that dHAND complexes with partners other than E-proteins in cardiac tissue. ..
  13. Morikawa Y, Cserjesi P. Cardiac neural crest expression of Hand2 regulates outflow and second heart field development. Circ Res. 2008;103:1422-9 pubmed publisher
    ..The basic helix-loop-helix factor Hand2 regulates development of cardiovascular structures and NC-derived tissues including those that contribute to face ..
  14. McFadden D, McAnally J, Richardson J, Charité J, Olson E. Misexpression of dHAND induces ectopic digits in the developing limb bud in the absence of direct DNA binding. Development. 2002;129:3077-88 pubmed
    ..eHAND and dHAND (also known as HAND1 and HAND2) are closely related bHLH proteins that control cardiac, craniofacial and limb development...
  15. Dai Y, Cserjesi P, Markham B, Molkentin J. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J Biol Chem. 2002;277:24390-8 pubmed
    ..GATA4 also interacts with the cardiac-expressed basic helix-loop-helix transcription factor dHAND (also known as HAND2)...
  16. Thomas T, Kurihara H, Yamagishi H, Kurihara Y, Yazaki Y, Olson E, et al. A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development. 1998;125:3005-14 pubmed
    ..Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome. ..
  17. Björck H, Renner J, Maleki S, Nilsson S, Kihlberg J, Folkersen L, et al. Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor. PLoS ONE. 2012;7:e52227 pubmed publisher
    ..The most differentially expressed gene, Hand2, is a transcription factor previously shown to be involved in extracellular matrix remodeling...
  18. Thomas T, Yamagishi H, Overbeek P, Olson E, Srivastava D. The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol. 1998;196:228-36 pubmed
  19. McFadden D, Barbosa A, Richardson J, Schneider M, Srivastava D, Olson E. The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner. Development. 2005;132:189-201 pubmed
    The basic helix-loop-helix transcription factors Hand1 and Hand2 display dynamic and spatially restricted expression patterns in the developing heart. Mice that lack Hand2 die at embryonic day 10...
  20. Barbosa A, Funato N, Chapman S, McKee M, Richardson J, Olson E, et al. Hand transcription factors cooperatively regulate development of the distal midline mesenchyme. Dev Biol. 2007;310:154-68 pubmed
    ..Hand1 is expressed in the distal (ventral) zone of the branchial arches, whereas the Hand2 expression domain extends ventrolaterally to occupy two-thirds of the mandibular arch...
  21. Funato N, Chapman S, McKee M, Funato H, Morris J, Shelton J, et al. Hand2 controls osteoblast differentiation in the branchial arch by inhibiting DNA binding of Runx2. Development. 2009;136:615-25 pubmed publisher
    ..Hand1 and Hand2 are expressed by a subset of neural crest cells in the anterior branchial arches and are involved in craniofacial ..
  22. Barnes R, Firulli B, Vandusen N, Morikawa Y, Conway S, Cserjesi P, et al. Hand2 loss-of-function in Hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development. Circ Res. 2011;108:940-9 pubmed publisher
    The basic helix-loop-helix (bHLH) transcription factors Hand1 and Hand2 are essential for embryonic development. Given their requirement for cardiogenesis, it is imperative to determine their impact on cardiovascular function...