Disease relevance of Po

• We also show that the increase in FGF signaling that occurs when the Fgf4 gain-of-function allele is activated in a wild-type limb bud causes formation of a supernumerary posterior digit (postaxial polydactyly), as well as cutaneous syndactyly between all the digits [1].
• Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma [2].
• Ectrodactyly, postaxial polydactyly, syndactyly, brachydactyly, adactyly, phocomelia, meromelia, and malrotation of the limbs were detected in a significant number of fetuses [3].

High impact information on Po

• Peripheral nerve myelin contains a dominant low molecular weight glycoprotein called Po [4].
• At all times examined, there was a single major peak of radioactivity that co-migrated on sodium dodecyl sulfate (SDS) acrylamide gels with the Po protein [4].
• The Po is in the open form when the Li is attached to an external high-affinity allosteric site on it [5].
• We found defects in external, middle and inner ear, reduction or loss of skull bones, a reduced and sometimes cleft mandible, and limb abnormalities including postaxial polydactyly and bent zeugopods [6].
• Postaxial polydactyly in forelimbs of CRABP-II mutant mice [7].

Biological context of Po

• Expression of myelin basic protein (MBP) and Po gene products is induced during the final postnatal maturation of Schwann cells and reinduced during nerve regeneration [8].
• Interestingly, SRC-1 levels are also positively correlated with Po gene expression independently of DHP exposure [9].
• In Po-DT-A mice, the defect is produced by a transgene using the rat Po promotor to direct the expression of gene encoding for the bacterial diphtherial toxin A chain (DT-A) [10].
• The human syntenic region of this locus has been previously linked to Meckel syndrome; the phenotype includes postaxial polydactyly, an ectopic digital defect hypothesized to be induced by a common molecular pathway with ectrodactyly [11].
• Previous experiments have demonstrated that oral administration of retinoic acid to ICR mice on day 10 of gestation results in an enhanced expression of postaxial polydactyly of the forelimbs [12].

Anatomical context of Po

• We show that a chimeric protein containing interleukin-6 fused to its soluble receptor (IL6RIL6 chimera) induces MBP and Po RNAs and proteins in cultures of dorsal root ganglia (DRG) from 14 day old mouse embryos [8].
• The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed [13].

Associations of Po with chemical compounds

• We found that SRC-1 overexpressing cells are more responsive to Po mRNA induction by DHP, whereas the effect of the steroid is completely lost in SRC-1-deficient cells [9].
• Po is known to be stimulated by progesterone and by its 5alpha-reduced metabolite, dihydroprogesterone (DHP), through the corresponding steroid receptor [9].

Other interactions of Po

• However, homozygous Msx1/Hx double mutants exhibit a postaxial polydactyly at birth, demonstrating that the two genes interact [14].
• Msx2-noggin mutant mice have severely malformed limbs characterized by syndactyly, postaxial polydactyly, and dorsal transformations of ventral structures indicated by absence of ventral footpads and presence of supernumerary ventral nails [15].
• In the forelimb autopod, pre- and postaxial polydactyly were found most commonly, but also syndactyly, oligodactyly, and abnormal digit placement affecting posterior elements were observed [16].
• The pad modifications in Hammertoe mice with webbed digits and postaxial polydactyly resemble closely those of the previously studied mice with genetic preaxial polydactyly [17].

References