  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 heart10 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.
