Retinoic acid controls early neurogenesis in the developing mouse cerebral cortex
Carole Haushalter1, Laure Asselin1, Valérie Fraulob1
1Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Centre National de la Recherche Scientifique, UMR 7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U 964, Illkirch, France; Université de Strasbourg, Illkirch, France.
Developmental Biology
|August 10, 2017
Summary
Retinoic acid (RA) is crucial for brain development. Its absence leads to reduced progenitor proliferation, premature neuron production, and microcephaly, impacting cerebral cortex formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Cerebral cortex development requires precise regulation of progenitor cell proliferation and differentiation.
- Retinoic acid (RA), a vitamin A derivative, is a signaling molecule in mammalian forebrain neurogenesis, but its precise role remains unclear.
- Studying RA's function is challenging due to early embryonic lethality in murine models of RA synthesis deficiency.
Purpose of the Study:
- To investigate the role of retinoic acid (RA) in mammalian corticogenesis, particularly at the onset of neurogenesis and during cortical layer establishment.
- To analyze the consequences of RA deficiency on progenitor cell behavior and neuronal production during embryonic development.
Main Methods:
- Analysis of corticogenesis in Rdh10 null mutant mice, which exhibit impaired RA synthesis.
- Examination of telencephalic vesicle size, cortical plate thickness, and progenitor cell dynamics at embryonic day 13.5.
- Assessment of radial glial (RG) cell proliferation, intermediate neuronal progenitor (INP) generation, and cell cycle exit.
Main Results:
- Rdh10 null mutants displayed smaller telencephalic vesicles and a reduced cortical plate thickness at embryonic day 13.5.
- In the absence of RA, RG progenitors showed decreased proliferation and premature neuronal production, leading to RG depletion by embryonic day 11.5.
- Lack of RA impaired INP generation and affected progenitor cell cycle exit, resulting in a deficit of projection neurons and microcephaly.
Conclusions:
- Retinoic acid (RA) is essential for regulating progenitor cell proliferation and differentiation during corticogenesis.
- RA deficiency disrupts the balance between proliferation and differentiation, leading to reduced neurogenesis and developmental defects like microcephaly.
- These findings highlight RA's critical role in establishing the correct number of projection neurons for proper brain development.
