The pattern of expression of the chicken homolog of HOX1I in the developing limb suggests a possible role in the ectodermal inhibition of chondrogenesis

Abstract

Homeobox-containing genes have been implicated in a variety of patterning events during vertebrate limb development. In an attempt to isolate cDNAs corresponding to 5' members of the chicken HOX 4 cluster of homeobox-containing genes, a cDNA library constructed from mRNAs expressed during early stages of chick limb development was screened with probes generated by the polymerase chain reaction (PCR) using oligonucleotide primers corresponding to sequences in the homeoboxes of the human HOX4C and HOX4F genes, the human homologs of Hox-4.4 and Hox-4.6. This screening resulted in the isolation of full length cDNAs for the chicken homolog of HOX4F (cognate of mouse Hox-4.6), which we have termed GHox-4.6, and the chicken homolog of human HOXlI, which we have named GHox-li, a paralog of Hox-4.6 in the HOX 1 cluster. The homeodomains encoded by GHox-4.6 and GHox-li differ by only three amino acids, and the two proteins show extensive similarity along their entire lengths. Despite their sequence similarity, in situ hybridization analysis has revealed that GHox-4.6 and GHox-li exhibit strikingly different spatial patterns of expression during embryonic chick limb development. At early stages of limb development (stages 20-22), GHox-4.6 transcripts are present in high amounts throughout the posterior half of the limb mesoderm and are absent from the anterior half of the mesoderm, an expression pattern consistent with the possible involvement of GHox-4.6 in the specification of posterior positional identity. In contrast, GHox-li exhibits no distinct anterior-posterior polarity of expression at stage 22, but rather is expressed in high amounts throughout the mesenchyme of the limb bud. At later stages of development (stage 25), GHox-li continues to be expressed in high amounts throughout the undifferentiated mesenchyme subjacent to the apical ectodermal ridge, and, in addition, is expressed in the mesodermal cells in the proximal peripheral regions of the limb bud subjacent to the ectoderm which are differentiating into nonchondrogenic lineages. bud where chondrogenic differentiation is occurring. Thus, GHox-li is expressed by the undifferentiated subridge mesenchymal cells and proximal peripheral mesenchymal cells of the limb bud that are being inhibited from undergoing chondrogenesis by the apical ectodermal ridge and nonridge ectoderm. These observations suggest the possibility that GHox-li may be involved in mediating the antichondrogenic effect of limb ectoderm, and that the cessation of GHox-li expression may be required for chondrogenic differentiation to occur in the proximal central core of the limb bud.

The homeobox transcription factor Barx2 regulates chondrogenesis during limb development

“…However, the identities most of the factors that bind to these motifs and their possible interactions with Sox proteins have not been elucidated. It is known that homeobox transcription factors, including members of the Hox, Msx and Dlx families, coordinate the expression of genes that are essential for differentiation of skeletal elements (Ferrari et al, 1994;Ferrari et al, 1995;Rogina et al, 1992;Satokata et al, 2000). Several lines of evidence also indicate that homeobox proteins are important transducers of BMP signaling pathways during chondrogenesis (Xu et al, 2001).…”

Testing the vulnerability of the phylotypic stage: On modularity and evolutionary conservation

“…Moreover, in the meantime evidence has accumulated that the temporal and spatial activation of Hox gene expression at other stages coincides less well with the order of the genes on the chromosomes. Important deviations from colinearity have evolved during hematopoiesis, limb, and skin development (e.g., Rogina et al, 1992;Gardiner, 1995;Nelson et al, 1996;Rijli and Chambon, 1997;Godwin and Capecci, 1998). For instance, in the skin some Hox genes are globally expressed whereas others are regionally restricted (Godwin and Capecci, 1998).…”

Stage‐ and region‐dependent chondrogenesis and growth of chick wing‐bud mesenchyme in serum‐containing and defined tissue culture media

“…Recently, immunohistochemistry and in situ hybridization have revealed tantalizing patterns of gene expression in the limb bud (Maden et al, 1988;Dolle et al, 1990;Izpisua-Belmonte et al, 1991;Yokouchi et al, 1991;Rogina et al, 1992;Ros et al, 1992). These patterns show limb mesenchyme to comprise a diverse cell population and may one day help explain skeletal pattern formation (Tabin, 1991(Tabin, ,1992.…”