Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations

Genesis. 2018 Jun;56(6-7):e23221. doi: 10.1002/dvg.23221.


Members of the large family of Hox transcription factors are encoded by genes whose tightly regulated expression in development and in space within different embryonic tissues confer positional identity from the neck to the tips of the limbs. Many structures of the face, head, and heart develop from cell populations expressing few or no Hox genes. Hoxb1 is the member of its chromosomal cluster expressed in the most rostral domain during vertebrate development, but never by the multipotent neural crest cell population anterior to the cerebellum. We have developed a novel floxed transgenic mouse line, CAG-Hoxb1,-EGFP (CAG-Hoxb1), which upon recombination by Cre recombinase conditionally induces robust Hoxb1 and eGFP overexpression. When induced within the neural crest lineage, pups die at birth. A variable phenotype develops from E11.5 on, associating frontonasal hypoplasia/aplasia, micrognathia/agnathia, major ocular and forebrain anomalies, and cardiovascular malformations. Neural crest derivatives in the body appear unaffected. Transcription of effectors of developmental signaling pathways (Bmp, Shh, Vegfa) and transcription factors (Pax3, Sox9) is altered in mutants. These outcomes emphasize that repression of Hoxb1, along with other paralog group 1 and 2 Hox genes, is strictly necessary in anterior cephalic NC for craniofacial, visual, auditory, and cardiovascular development.

Keywords: cleft palate; double outlet right ventricle; exencephaly; mandibular agenesis; maxillary aplasia; valve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / physiology
  • Cell Movement
  • Craniofacial Abnormalities / embryology
  • Craniofacial Abnormalities / genetics*
  • Ectopic Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Genes, Homeobox / genetics
  • Head / embryology
  • Heart / embryology
  • Heart Defects, Congenital / embryology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Neural Crest / metabolism
  • Signal Transduction


  • HOXB1 homeodomain protein
  • Homeodomain Proteins