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Smad3 Deficiency Reduces Neurogenesis in Adult Mice

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Abstract

Transforming growth factor-β signaling through Smad3 inhibits cell proliferation in many cell types. As cell proliferation in the brain is an integral part of neurogenesis, we sought to determine the role of Smad3 in adult neurogenesis through examining processes and structures important to neurogenesis in adult Smad3 null mice. We find that there are fewer proliferating cells in neurogenic regions of adult Smad3 null mouse brains and reduced migration of neuronal precursor cells from the subventricular zone to the olfactory bulb. Alterations in astrocyte number and distribution within the rostral migratory stream of Smad3 null mice give rise to a smaller and more disorganized structure that may impact on neuronal precursor cell migration. However, the proportion of proliferating cells that become neurons is similar in wild type and Smad3 null mice. Our results suggest that signaling through Smad3 is needed to maintain the rate of cell division of neuronal precursors in the adult brain and hence the amount of neurogenesis, without altering neuronal cell fate.

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Acknowledgements

We thank Dr. Chuxia Deng (NIH) for supplying the Smad3 null mice and are grateful for the encouragement and support we received from Dr. Anita Roberts when first starting this project. We thank Helina Moges and Matthew Adams for significant technical assistance and past and present members of the Symes lab for their helpful comments and suggestions. This work was supported by a translational research grant from the Defense Brain and Spinal Cord Injury Program (AJS). The opinions and assertions contained herein are the private opinions of the authors and are not to be construed as reflecting the views of the Uniformed Services University of the Health Sciences, the US Department of Defense, or the Government of the USA.

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  1. Yu Wang

    Present address: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, 210 Jixi Road, Hefei, 230022, China

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  1. Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA

    Yu Wang & Aviva J. Symes

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Wang, Y., Symes, A.J. Smad3 Deficiency Reduces Neurogenesis in Adult Mice. J Mol Neurosci 41, 383–396 (2010). https://doi.org/10.1007/s12031-010-9329-x

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