Many genes that control pattern formation in insects contain a conserved homeobox region which encodes a domain involved in DNA binding. One approach to understanding pattern formation in vertebrates is to examine the role of homeobox-containing genes in the developing limb. Two such genes, Hox-7.1 and Hox-8.1, are expressed in distal mesoderm, but not in the proximal core, of mouse forelimb (refs 3, 4, and D.R.D., manuscript in preparation). The proximodistal cartilage pattern in the chick wing is progressively determined in the distal mesoderm, which is maintained as a 'progress zone' by the overlying apical ectodermal ridge. Indeed, proximal cells are reprogrammed to form distal structures when placed in the progress zone and we therefore expect that genes involved in controlling limb pattern should be activated in such grafts. We tested this requirement for Hox-7.1 and Hox-8.1 in mouse limb mesoderm placed in chick wing buds. Our results reported here indicate that both genes are rapidly activated by a signal from the apical ectoderm. These properties, taken with the DNA-binding properties of the homeodomain, strongly suggest that Hox-7.1 and Hox-8.1 have fundamental roles in limb-pattern formation.
Two retinoids, all-trans-retinoic acid and a synthetic analog, TTNPB, were locally applied to different positions along the proximo-distal axis of embryonic chick wing buds using controlled release carriers. Truncations or limbs with duplicated structures across the antero-posterior axis develop after retinoid application to distal positions in buds from stage 20-24 embryos. Phocomelic limbs develop when the retinoids are applied more proximally to buds of stage 23-24 embryos. Duplications of the pattern of structures along the proximo-distal axis never occur.Using TTNPB that is relatively stable, the amount of retinoid in the wing tissue when phocomelia is induced was measured. There is twice as much retinoid per cell in the proximal half of the bud as in the distal half of the bud. The concentration of TTNPB in proximal tissue is estimated to be three times higher than in distal tissue in which pattern formation and cartilage morphogenesis are relatively normal.At early stages in the development of phocomelia, the shape of the bud changes and the indentation that marks the elbow does not arise. Neither retinoid-induced cell killing nor effects on the pattern of programmed cell death were detected.The induction of phocomelia by retinoids appears to be based on effects on proximal cells, whereas retinoids produce pattern changes by acting on distal cells. Furthermore, compared with pattern changes, higher concentrations of retinoid in the bud tissue are required to produce phocomelia.
Mll, Brg1 and Brm are vertebrate homologues of Drosophila trithorax group (trxG) genes. We isolated chicken Mll cDNA clones, and examined patterns of Mll, Brg1 and Brm expression in chick embryos. All three genes were expressed from embryonic stage 2 onwards. Mll transcripts were just detectable in all tissues by in situ hybridization, with highest level in dorsal neural tube and notochord. Brg1 transcripts were readily detectable in all tissues, with highest levels in dorsal neural tube, dorsal trunk epithelium and limb bud epithelium and mesenchyme. Brm transcripts were more restricted, being found in dermomyotome, notochord, dorsal limb bud epithelium, eye and the roof and floor plates of the neural tube.
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