Gene Symbol: Alx3
Description: aristaless-like homeobox 3
Alias: homeobox protein aristaless-like 3, proline-rich transcription factor Alx3
Species: mouse
Products:     Alx3

Top Publications

  1. Beverdam A, Brouwer A, Reijnen M, Korving J, Meijlink F. Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. Development. 2001;128:3975-86 pubmed
    ..We have generated an Alx3 mutant allele in which the lacZ coding sequence is inserted in-frame in the Alx3 gene and the sequences encoding ..
  2. ten Berge D, Brouwer A, el Bahi S, Guenet J, Robert B, Meijlink F. Mouse Alx3: an aristaless-like homeobox gene expressed during embryogenesis in ectomesenchyme and lateral plate mesoderm. Dev Biol. 1998;199:11-25 pubmed
    Mouse Alx3 is a homeobox gene that is related to the Drosophila aristaless gene and to a group of vertebrate genes including Prx1, Prx2, Cart1, and Alx4...
  3. Beverdam A, Meijlink F. Expression patterns of group-I aristaless-related genes during craniofacial and limb development. Mech Dev. 2001;107:163-7 pubmed
  4. Lakhwani S, García Sanz P, Vallejo M. Alx3-deficient mice exhibit folic acid-resistant craniofacial midline and neural tube closure defects. Dev Biol. 2010;344:869-80 pubmed publisher
    ..We report that folic acid is required in mouse embryos for the specific expression of the homeodomain gene Alx3 in the head mesenchyme, an important tissue for cranial neural tube closure...
  5. Compagnucci C, Fish J, Schwark M, Tarabykin V, Depew M. Pax6 regulates craniofacial form through its control of an essential cephalic ectodermal patterning center. Genesis. 2011;49:307-25 pubmed publisher
    ..Pax6 therefore regulates craniofacial form, at stages when CNC has just arrived in the frontonasal region, through its control of surface cephalic ectodermal competence to form an essential craniofacial patterning center. ..
  6. Griffin J, Compagnucci C, Hu D, Fish J, Klein O, Marcucio R, et al. Fgf8 dosage determines midfacial integration and polarity within the nasal and optic capsules. Dev Biol. 2013;374:185-97 pubmed publisher
    ..Taken together, our data highlight Fgf8 signaling in craniofacial development as a plausible target for evolutionary selective pressures...
  7. Manley N, Barrow J, Zhang T, Capecchi M. Hoxb2 and hoxb4 act together to specify ventral body wall formation. Dev Biol. 2001;237:130-44 pubmed
    ..5, before secondary body wall formation. Prior to this defect, both Alx3 and Alx4 were specifically down regulated in the most ventral part of the primary body wall in Hoxb4(PolII) mutants...
  8. Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, et al. SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell. 2006;125:971-86 pubmed
    ..Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation...
  9. Ko S, Chung I, Xu X, Oka S, Zhao H, Cho E, et al. Smad4 is required to regulate the fate of cranial neural crest cells. Dev Biol. 2007;312:435-47 pubmed
    ..Taken together, our data show that TGF-beta/BMP signals rely on Smad-dependent pathways in the ectomesenchyme to mediate epithelial-mesenchymal interactions that control craniofacial organogenesis...

More Information


  1. Xu J, Krebs L, Gridley T. Generation of mice with a conditional null allele of the Jagged2 gene. Genesis. 2010;48:390-3 pubmed publisher
    ..This Jag2 conditional null allele will enable investigation of Jag2 function in a variety of tissue-specific contexts. ..
  2. Vallejo M. The aristaless-like homeobox protein Alx3 as an etiopathogenic factor for diabetes mellitus. Islets. 2011;3:66-8 pubmed
    Inactivation of the gene encoding the aristaless-related homeodomain transcription factor Alx3 results in islet cell apoptosis and impaired glucose homeostasis that worsens with age due to the appearance of insulin resistance...
  3. McGonnell I, Graham A, Richardson J, Fish J, Depew M, Dee C, et al. Evolution of the Alx homeobox gene family: parallel retention and independent loss of the vertebrate Alx3 gene. Evol Dev. 2011;13:343-51 pubmed publisher
    ..common ancestor of jawed vertebrates had three Alx genes descendent from the two-round genome duplications (Alx1, Alx3, Alx4), compared with a single amphioxus gene...
  4. Loebel D, O Rourke M, Steiner K, Banyer J, Tam P. Isolation of differentially expressed genes from wild-type and Twist mutant mouse limb buds. Genesis. 2002;33:103-13 pubmed
    ..We show that the aristaless-like transcription factors, Alx3 and Alx4 are downregulated in the Twist(-/-) mutant and may be potential targets of Twist...
  5. Kur E, Mecklenburg N, Cabrera R, Willnow T, Hammes A. LRP2 mediates folate uptake in the developing neural tube. J Cell Sci. 2014;127:2261-8 pubmed publisher
    ..Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants...
  6. He F, Soriano P. A critical role for PDGFR? signaling in medial nasal process development. PLoS Genet. 2013;9:e1003851 pubmed publisher
    ..We thus establish PDGFR? as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels. ..
  7. Yamada R, Mizutani Koseki Y, Koseki H, Takahashi N. Requirement for Mab21l2 during development of murine retina and ventral body wall. Dev Biol. 2004;274:295-307 pubmed
    ..Our results reveal that Mab21l2 plays crucial roles in retina and in ventral body wall formation. ..
  8. Matsumoto T, Yamada A, Aizawa R, Suzuki D, Tsukasaki M, Suzuki W, et al. BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation. PLoS ONE. 2013;8:e68774 pubmed publisher
    ..We focused on Alx3 (aristaless-like homeobox 3) which was clearly induced during osteoblast differentiation...
  9. Bildsoe H, Loebel D, Jones V, Chen Y, Behringer R, Tam P. Requirement for Twist1 in frontonasal and skull vault development in the mouse embryo. Dev Biol. 2009;331:176-88 pubmed publisher
    ..In contrast, the formation of other mesodermal skeletal derivatives such as the occipital bones and most of the chondrocranium are not affected by the loss of Twist1 in the neural crest cells. ..
  10. Mirasierra M, Fernandez Perez A, Díaz Prieto N, Vallejo M. Alx3-deficient mice exhibit decreased insulin in beta cells, altered glucose homeostasis and increased apoptosis in pancreatic islets. Diabetologia. 2011;54:403-14 pubmed publisher
    ..In previous studies we determined that aristaless-like homeobox 3 (ALX3) is produced in islet cells, binds to the promoter of the insulin gene and regulates its expression...
  11. Zhang Y, Blackwell E, McKnight M, Knutsen G, Vu W, Ruest L. Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with hand2. Dev Dyn. 2012;241:924-40 pubmed publisher
    ..To determine the role of Twist1 during mandibular development, we used the Hand2-Cre transgene to conditionally inactivate the gene in the neural crest cells populating the mandibular pharyngeal arch...
  12. Brunskill E, Potter A, Distasio A, Dexheimer P, Plassard A, Aronow B, et al. A gene expression atlas of early craniofacial development. Dev Biol. 2014;391:133-46 pubmed publisher
  13. Mirasierra M, Vallejo M. Glucose-dependent downregulation of glucagon gene expression mediated by selective interactions between ALX3 and PAX6 in mouse alpha cells. Diabetologia. 2016;59:766-75 pubmed publisher
    ..Here, we investigated the role of the transcription factor aristaless-like homeobox 3 (ALX3) as a glucose-dependent modulator of PAX6 activity in alpha cells...
  14. García Sanz P, Fernandez Perez A, Vallejo M. Differential configurations involving binding of USF transcription factors and Twist1 regulate Alx3 promoter activity in mesenchymal and pancreatic cells. Biochem J. 2013;450:199-208 pubmed publisher
    During embryonic development, the aristaless-type homeodomain protein Alx3 is expressed in the forehead mesenchyme and contributes to the regulation of craniofacial development...
  15. Kuijper S, Beverdam A, Kroon C, Brouwer A, Candille S, Barsh G, et al. Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes. Development. 2005;132:1601-10 pubmed
  16. Hirota J, Mombaerts P. The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons. Proc Natl Acad Sci U S A. 2004;101:8751-5 pubmed
    ..OSN development appears to be arrested between the terminal differentiation into neurons and the transition to immature neurons. Thus, Lhx2 is required for complete development of OSNs in mice. ..
  17. ten Berge D, Brouwer A, Korving J, Reijnen M, van Raaij E, Verbeek F, et al. Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis. Development. 2001;128:2929-38 pubmed
    ..In addition, this treatment led to loss of the mandibular incisors. We present a model that describes how loss of Shh expression in Prx1(-/-)Prx2(-/-) mutants leads to abnormal morphogenesis of the mandibular arch. ..
  18. O Rourke M, Soo K, Behringer R, Hui C, Tam P. Twist plays an essential role in FGF and SHH signal transduction during mouse limb development. Dev Biol. 2002;248:143-56 pubmed
    ..with SHH signalling in the limb bud mesenchyme, the down-regulation of Bmp4 in the apical ectoderm, the absence of Alx3, Alx4, Pax1, and Pax3 activity in the mesenchyme, and a reduced potency of the limb bud tissues to differentiate ..
  19. Fernandez Perez A, Vallejo M. Pdx1 and USF transcription factors co-ordinately regulate Alx3 gene expression in pancreatic ?-cells. Biochem J. 2014;463:287-96 pubmed publisher
    ..The homeodomain transcription factor Alx3 (aristaless-like homeobox 3) expressed in pancreatic islets participates in the regulated expression of several ..
  20. Meijlink F, Beverdam A, Brouwer A, Oosterveen T, Berge D. Vertebrate aristaless-related genes. Int J Dev Biol. 1999;43:651-63 pubmed