Smad3 deficiency reduces neurogenesis in adult mice.
Transforming growth factor-beta 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.
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Yu
Y
Wang
Aviva J
AJ
Symes
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051900:Smad3 Protein / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
D051900:Smad3 Protein; C497791:Smad3 protein, mouse