Disease relevance of al

• Most strikingly, however, 90% of heterozygous mice were reported to develop multiple intestinal adenomatous polyps, most notably in the proximal colon (Chawengsaksophak et al., 1997) [1].
• Mutations in the highly conserved Aristaless-related homeodomain protein ARX have been shown to underlie multiple forms of X-linked mental retardation [2].

High impact information on al

• Ectopic expression of wg can induce both ectopic al expression and a duplication of the proximodistal axis (the development of supernumerary legs), but only in regions expressing high levels of dpp [3].
• The proximodistal axis may be specified via a mechanism involving a direct interaction between cells expressing wg, dpp, and possibly al [3].
• Driever et al. proposed that at least one other bcd-activated gene controls the development of head regions anterior to the hb domain [4].
• The al gene contains a prd-type homeo domain and a Pro/Gln-rich domain and, hence, probably encodes a transcription factor [5].
• The al gene is also transcribed during embryogenesis [5].

Biological context of al

• The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila [6].
• The al gene has been cloned and identified by P-element-mediated germ-line transformation with a genomic DNA fragment, which rescues a lethal mutation of al as well as aspects of the adult al phenotype [5].
• So far, only partial nucleotide sequences have been reported for mouse Hoxa-9 cDNA (Rubin et al., (1987) Mol. Cell. Biol. 7, 3836-3841) [7].
• Finally, we have molecularly characterized an enhancer trap line, AE33, that was identified in earlier screens as a target of both ro and gl (freeman et al., 1992; Treisman and Rubin, 1996) [8].
• Mammalian alpha-adaptins are encoded by two genes; however, Drosophila alpha-adaptin has a single gene locus, within polytene bands 21C2-C3 on the left arm of the chromosome 2, closely adjacent to the paired homeobox gene aristaless [9].

Anatomical context of al

• Tarsus/pretarsus boundary formation requires at least two different Bar functions, early antagonistic interactions with a pretarsus-specific homeobox gene, aristaless, and the subsequent induction of Fas II expression in pretarsus cells abutting tarsal segment 5 [10].
• Mouse Alx3: an aristaless-like homeobox gene expressed during embryogenesis in ectomesenchyme and lateral plate mesoderm [11].
• Previously, we have identified three highly-related genes of the mouse Iroquois gene family that exert specific expression patterns in the central nervous system (A. Bosse et al., Mech Dev 69:169-181, 1997) [12].

Regulatory relationships of al

• C15 is expressed in the same cells as al and, together, C15 and Al appear to directly repress B [13].

Other interactions of al

• Here, the roles played by al and Dll in patterning the legs and wings have been investigated through loss of function studies [6].
• No Lim1 misexpression occurred upon aristaless misexpression [14].
• The most frequent recombinant phenotype observed was b cn followed by cn and al [15].
• The P11 sequence corresponds to the Hrb87F sequence that was recently described by Haynes et al [16].
• The homeobox-containing gene tinman (msh-2, Bodmer et al., 1990 Development 110, 661-669) is expressed in the mesoderm primordium, and this expression requires the function of the mesoderm determinant twist [17].

References