The mouse bagpipe gene controls development of axial skeleton, skull, and spleen

Abstract

The mouse Bapx1 gene is homologous to the Drosophila homeobox containing bagpipe (bap) gene. A shared characteristic of the genes in these two organisms is expression in gut mesoderm. In Drosophila, bap functions to specify the formation of the musculature of the midgut. To determine the function of the mammalian cognate, we targeted a mutation into the Bapx1 locus. Bapx1, similar to Drosophila, does have a conspicuous role in gut mesoderm; however, this appears to be restricted to development of the spleen. In addition, Bapx1 has a major role in the development of the axial skeleton. Loss of Bapx1 affects the distribution of sclerotomal cells, markedly reducing the number that appear ventromedially around the notochord. Subsequently, the structures in the midaxial region, the intervertebral discs, and centra of the vertebral bodies, fail to form. Abnormalities are also found in those bones of the basal skull (basioccipital and basisphenoid bones) associated with the notochord. We postulate that Bapx1 confers the capacity of cells to interact with the notochord, effecting inductive interactions essential for development of the vertebral column and chondrocranium.

Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network

“…Mutations in FoxF TFs cause defects in gut muscle differentiation in both mice (Mahlapuu et al 2001a;Wang et al 2003;Ormestad et al 2004Ormestad et al , 2006 and Xenopus (Tseng et al 2004), similar to those observed in flies (Zaffran et al 2001). Likewise, BapX is required for the specification of subtypes of VM in mice (Lettice et al 1999) and flies (Azpiazu and Frasch 1993). This high level of functional conservation suggests that the underlying transcriptional circuitry governing VM development may also be conserved.…”

Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation

“…Further analysis will be required for understanding the molecular mechanisms underlying this gastroduodenal defect observed in Bapx1 mutants. Mutant mice with an insertion mutation of Bapx1 was recently reported (Lettice et al 1999), in which neomycin-resistant cassette was inserted in the 5 H exon. From that allele, an aberrantly spliced transcript, corresponding to the 3 H coding region of Bapx1, was ampli®ed at low level by RT-PCR.…”

Roles of the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis

“…One potential explanation for this discrepancy is the possibility that there is partial genetic redundancy between Nkx3.1 and Nkx3.2, which have overlapping expression domains in the paraxial mesoderm. In particular, Nkx3.2 is expressed in the sclerotomal region of the developing somite and subsequently in nascent cartilage (Tribioli et al, 1997), and loss of Nkx3.2 function results in absence of the ventromedial region of the vertebral column (Lettice et al, 1999;Tribioli and Lufkin, 1999;Akazawa et al, 2000). Another possibility is that there is functional redundancy even in tissues with nonoverlapping expression of Nkx3.1 and Nkx3.2.…”