The limb deformity gene is required for apical ectodermal ridge differentiation and anteroposterior limb pattern formation.

Abstract

To gain insight into the role of the limb deformity [Id] gene in limb morphogenesis, we examined the morphologic details of early embryonic limb formation in the mutant Id/ld mouse. Initial morphological differences between wild-type and homozygous Id embryos are apparent during early gestational day 10, a time period during which anteroposterior limb morphogenesis occurs. As a result of a shortened anteroposterior axis, the mutant limb bud appears more pointed than its wild-type counterpart. In addition, the apical ectodermal ridge (AER), a structure crucial to both proximodistal and anteroposterior limb development, fails to differentiate properly in mutant Id embryos. Consistent with these observations, molecular analysis of the limb promordia shows that the limb ectoderm contains a level of Id transcripts fivefold higher relative to its mesenchyme. Furthermore, expression of Id transcripts in other parts of the developing embryo and in primitive streak embryos (gestational day 7) suggests possible roles for this gene in the earliest determinative events of morphogenesis. These data lead us to conclude that Id gene products are required for both proper AER differentiation and anteroposterior pattern formation in limb mesenchyme.

Limb deformity proteins during avian neurulation and sense organ development

“…In the kidney, expression was detected in the epithelial compartment of the kidney rudiments from the earliest developmental time point onwards. These results, together with the nature of the murine Id phenotype (Zeller et al, 1989;Maas et al, 1994) indicated a role for the nuclear Ld proteins in the earliest determinative interactions that regulate limb and kidney morphogenesis. The differential distribution observed in the notochord, neural tube and other embryonic structures suggested additional roles for Id gene products in motor neuron formation and morphogenesis of mesodermal derivatives (Trumpp et al, 1992).…”

“…More importantly, it indicates that the Ld proteins have probably more general roles during pattern formation and differentiation than presently assumed. Therefore, a true loss-of-function mutation in the Id gene could cause a much earlier and severe embryonic phenotype than expected from analysis of the existing, probably hypomorphic murine Id alleles (Kleinebrecht et al, 1982;Zeller et al, 1989;Maas et al, 1990Maas et al, , 1994.…”

“…Five independent alleles of the Id mutation have been identified to date and all cause a pleiotropic mutant phenotype affecting morphogenesis of limbs and kidneys (Cupp, 1960;Green, 1962;Kleinebrecht et al, 1982;Woychik et al, 1985Woychik et al, , 1990a and results in shortening of the antero-posterior limb axis (Zeller et al, 1989). Limb pattern formation is severely affected and results in deletions and fusions of limb skeletal elements along the antero-posterior axis.…”

“…Both the AER and ureteric bud are mediators of the epithelialmesenchymal interactions that control patterning of the limb and the kidney, respectively. The Id phenotype implies a crucial role of Id gene products in the molecular network regulating these epithelial-mesenchymal interactions (Zeller et al, 1989;Maas et al, 1994).…”

“…The Id gene spans at least 200 kb and encodes alternatively processed transcripts expressed in specific embryonic and adult tissues (Zeller et al, 1989;Woychik et al, 1990b;Jackson-Grusby et al, 1992). These different transcripts encode long open reading frames (ORFs) that create a family of related proteins.…”