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Disruption of local retinoid-mediated gene expression accompanies abnormal development in the mammalian olfactory
R M Anchan1, D P Drake, C F Haines
1Department of Neurobiology, Duke University Medical School, Durham, North Carolina 27710, USA.
Abstract:
We have evaluated the role of retinoid signaling in the early development of the olfactory epithelium and olfactory bulb. When retinoid-mediated gene expression is blocked briefly in mouse embryos at midgestation with citral (a general alcohol dehydrogenase antagonist that is thought to interfere with retinoid synthesis), the spectrum of morphogenetic abnormalities includes disruption of olfactory pathway development. It is difficult, however, to assess the specificity of this pharmacological manipulation, insofar as it also compromises several other aspects of central nervous system development. In homozygous Pax6 mutant mice (small eye: Pax6(Sey-Neu)), there is a more discrete lesion to the olfactory pathway: The epithelium and bulb cannot be recognized at any time during development, whereas other forebrain subdivisions can still be recognized. This loss of the entire primary olfactory pathway is accompanied by a failure of retinoid-mediated gene expression limited to the frontonasal region and forebrain. Retinoid receptors are expressed in the forebrain of Pax6(Sey-Neu)/Pax6(Sey-Neu) embryos, and the mutant forebrain remains responsive to exogenous retinoic acid. However, in Pax6(Sey-Neu)/ Pax6(Sey-Neu) embryos, retinoic acid (RA) is not produced by the frontonasal mesenchyme, which normally provides local retinoid signals to the placode and forebrain. Together, these results suggest that local retinoid signaling is essential for the normal development of the mammalian olfactory pathway.
Insights
Retinoid signaling is crucial for developing the olfactory system in mice. Disruption of this pathway, particularly in Pax6 mutant embryos, leads to the complete loss of the olfactory epithelium and bulb, highlighting retinoids
Area of Science:
- Developmental Biology
- Neuroscience
- Genetics
Background:
- Retinoid signaling plays a vital role in embryonic development.
- The development of the olfactory system is complex and requires precise molecular cues.
Purpose of the Study:
- To investigate the role of retinoid signaling in the development of the olfactory epithelium and olfactory bulb.
- To determine the specific contribution of retinoids to olfactory pathway formation.
Main Methods:
- Pharmacological inhibition of retinoid synthesis using citral in mouse embryos.
- Analysis of homozygous Pax6 mutant mice (Pax6(Sey-Neu)) to assess olfactory pathway development.
- Examination of retinoid-mediated gene expression and retinoic acid production in mutant embryos.
Main Results:
- Pharmacological blockade of retinoid signaling disrupted olfactory pathway development.
- Pax6 mutant mice exhibited a complete absence of the olfactory epithelium and bulb.
- Retinoid signaling failure in Pax6 mutants was localized to the frontonasal region and forebrain.
- Retinoic acid production by the frontonasal mesenchyme was absent in Pax6 mutants.
Conclusions:
- Local retinoid signaling is essential for the normal development of the mammalian olfactory pathway.
- Pax6 plays a critical role in regulating retinoid production necessary for olfactory system formation.