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Aldehyde dehydrogenase 6, a cytosolic retinaldehyde dehydrogenase prominently expressed in sensory neuroepithelia
1Institute for Virus Research, Kyoto University, 53 Kawaramachi Shogoin, Kyoto, Japan.
Insights
We identified chick and mouse aldehyde dehydrogenase 6 (ALDH6), crucial for retinaldehyde metabolism. Its expression in sensory neuroepithelia suggests a role in retinoic acid signaling during early neurodevelopment.
Area of Science:
- Biochemistry
- Developmental Biology
- Neuroscience
Background:
- Aldehyde dehydrogenase 6 (ALDH6) is a cytosolic enzyme involved in retinaldehyde metabolism.
- Understanding ALDH6's role is crucial for comprehending retinoid signaling pathways.
Purpose of the Study:
- To isolate and characterize chick and mouse homologs of human ALDH6.
- To investigate the expression patterns and functional significance of ALDH6 in embryonic development.
Main Methods:
- Isolation and characterization of ALDH6 homologs from chick and mouse.
- In situ hybridization to determine gene expression localization.
- Enzyme kinetics assays for recombinant ALDH6.
- Transient transfection experiments to assess functional impact on retinoic acid signaling.
Main Results:
- Chick and mouse ALDH6 homologs were successfully isolated.
- Strong ALDH6 expression was observed in sensory neuroepithelia of the head (eye, nose, ear) in both species.
- ALDH6 demonstrated high affinity and cooperativity for all-trans-retinaldehyde.
- ALDH6 expression enhanced retinoic acid receptor-dependent signaling.
Conclusions:
- ALDH6 plays a significant role in retinaldehyde metabolism during embryonic development.
- Its localization suggests a critical function in retinoic acid signaling within the developing sensory neuroepithelia and central nervous system.
- ALDH6 is implicated in primary neurogenesis at key sensory and neural sites.
Abstract:
We have isolated the chick and mouse homologs of human aldehyde dehydrogenase 6 (ALDH6) that encode a third cytosolic retinaldehyde-specific aldehyde dehydrogenase. In both chick and mouse embryos, strong expression is observed in the sensory neuroepithelia of the head. In situ hybridization analysis in chick shows compartmentalized expression primarily in the ventral retina, olfactory epithelium, and otic vesicle; additional sites of expression include the isthmus, Rathke's pouch, posterior spinal cord interneurons, and developing limbs. Recombinant chick ALDH6 has a K(0.5) = 0.26 microm, V(max) = 48.4 nmol/min/mg and exhibits strong positive cooperativity (H = 1.9) toward all-trans-retinaldehyde; mouse ALDH6 has similar kinetic parameters. Expression constructs can confer 1000-fold increased sensitivity to retinoic acid receptor-dependent signaling from retinol in transient transfections experiments. The localization of ALDH6 to the developing sensory neuroepithelia of the eye, nose, and ear and discreet sites within the CNS suggests a role for RA signaling during primary neurogenesis at these sites.