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.
Department of Ophthalmology, Lied Transplant Center, University of Nebraska Medical Center, Omaha 68198-7691, USA.
Ani V
AV
Das
Jackson
J
James
Xing
X
Zhao
Jörg
J
Rahnenführer
Iqbal
I
Ahmad
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