Limb and lower-body duplications induced by retinoic acid in mice
- Univ. of Washington, Seattle, WA (United States)
- Oak Ridge National Lab., TN (United States)
- Univ. of Washington School of Medicine, Seattle, WA (United States)
- Oberlin College, OH (United States)
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, the authors treated pregnant mice with trans-retinoic acid, a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. Trans-Retinoic acid induced a distinctive set of malformations, as manifested by supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period of 4.5-5.5 days after mating (other malformations were induced at different stages). The limb and lower-body duplications suggest that exogenous trans-retinoic acid may influence not only the pattern for the hindlimbs but also that for the entire lower body. Since it appears likely that the embryos were affected in the late blastocyst and proamniotic-embryo stages, the provocative possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation.
- DOE Contract Number:
- AC05-84OR21400
- OSTI ID:
- 6792631
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 91:12; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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