Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling.
Neural stem cells are present in specific regions of the adult central nervous system (CNS). Recent evidence suggests that the ciliary epithelium (CE), a CNS derivative, in the adult mammalian eye, harbors a quiescent population of neural stem cells. Here, we report the identification of c-Kit signaling as one of the regulators of adult CE neural stem cells in vitro. c-Kit receptors are expressed in proliferating adult CE neural stem cells and colocalized with neural progenitor markers. Perturbation of c-Kit signaling influences the self-renewal and differentiation of CE neural stem cells, thus demonstrating the role of c-Kit signaling in the maintenance of these cells. In addition, we observed an influence of c-Kit-mediated signaling on the expression of Notch1, another critical regulator of neural stem cells. Our observations suggest that, given the importance of preservation of a stem cell pool for generating different cell types at different times, multiple signaling pathways act in concert for the maintenance of neural stem cells.
Das
Ani V
AV
Department of Ophthalmology, Lied Transplant Center, University of Nebraska Medical Center, Omaha 68198-7691, USA.
James
Jackson
J
Zhao
Xing
X
Rahnenführer
Jörg
J
Ahmad
Iqbal
I
D000818:Animals; D001973:Bromodeoxyuridine; D002924:Ciliary Body / Q000166:cytology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins; D040081:Protein Array Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D051381:Rats; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014404:Tubulin
D017931:DNA Primers; D018076:DNA, Complementary; D008164:Luminescent Proteins; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014404:Tubulin; D049452:Green Fluorescent Proteins; D012313:RNA; D019009:Proto-Oncogene Proteins c-kit; D001973:Bromodeoxyuridine