Autoregulation of neurogenesis by GDF11.
In the olfactory epithelium (OE), generation of new neurons by neuronal progenitors is inhibited by a signal from neurons themselves. Here we provide evidence that this feedback inhibitory signal is growth and differentiation factor 11 (GDF11). Both GDF11 and its receptors are expressed by OE neurons and progenitors, and GDF11 inhibits OE neurogenesis in vitro by inducing p27(Kip1) and reversible cell cycle arrest in progenitors. Mice lacking functional GDF11 have more progenitors and neurons in the OE, whereas mice lacking follistatin, a GDF11 antagonist, show dramatically decreased neurogenesis. This negative autoregulatory action of GDF11 is strikingly like that of its homolog, GDF8/myostatin, in skeletal muscle, suggesting that similar strategies establish and maintain proper cell number during neural and muscular development.
Wu
Hsiao-Huei
HH
Department of Anatomy and Neurobiology and The Developmental Biology Center, University of California, Irvine, Irvine, CA 92697, USA.
Ivkovic
Sanja
S
Murray
Richard C
RC
Jaramillo
Sylvia
S
Lyons
Karen M
KM
Johnson
Jane E
JE
Calof
Anne L
AL
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005246:Feedback / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D038681:Follistatin / Q000502:physiology; D055412:Growth Differentiation Factors; D006706:Homeostasis / Q000502:physiology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D009420:Nervous System / Q000254:growth & development*; D009831:Olfactory Mucosa / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000502:physiology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics
D019485:Bone Morphogenetic Proteins; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D038681:Follistatin; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27