Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property.
Signaling through the Notch pathway regulates multiple aspects of development. The vertebrate retina allows an investigation of the basis for these various effects, because the major cell types of the retina arise from a common progenitor that expresses Notch1. The Notch pathway was constitutively activated in distinct populations of retinal cells during development. Prolonged Notch activity in progenitor cells maintained cells in the progenitor state without perturbing temporal identity, promoting early progenitor characteristics early in development and late progenitor characteristics later in development. Eventually, constitutive Notch activation led these cells to acquire characteristics of glial and stem cells. In contrast, reactivating the Notch pathway in newly postmitotic retinal cells promoted mature glial cell formation in a subset of cells. These data suggest that prolonged Notch activity does not disrupt the normal progression of progenitor temporal states, and that down-regulating or overcoming Notch activity is required for proper formation of both neuronal and glial cell fates.
Jadhav
Ashutosh P
AP
Division of Health Sciences and Technology, Department of Genetics, Harvard-Massachusetts Institute of Technology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cho
Seo-Hee
SH
Cepko
Constance L
CL
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051880:Receptors, Notch; C465570:Shh protein, mouse; D014157:Transcription Factors; C088975:Vsx2 protein, mouse