The canonical Wnt pathway regulates retinal stem cells/progenitors in concert with Notch signaling.
The canonical Wnt pathway is known to influence multiple developmental events such as patterning, cell proliferation and cell specification. Recent studies have provided evidence of the involvement of the canonical Wnt pathway in the emergence and development of the optic neuroepithelium and its derivatives, particularly the retina. However, the mechanism of its action during retinal development remains rather obscure. Here, we demonstrate that (in agreement with observations in the blood, intestine, and skin) the canonical Wnt pathway influences retinal development by maintaining stem cells/progenitors. For example, the activation of this pathway keeps the early retinal stem cells/progenitors proliferating and uncommitted, while its attenuation facilitates their differentiation into retinal ganglion cells in vitro and in vivo. In addition, we demonstrate that Wnt signaling acts in concert with Notch signaling during retinal histogenesis, where the latter calibrates the influence of the former on the differentiation status of retinal stem cells/progenitors by regulating Lef1 and sFRP2.
Das
Ani V
AV
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5840, USA.
Bhattacharya
Sumitra
S
Zhao
Xing
X
Hegde
Ganapati
G
Mallya
Kavita
K
Eudy
James D
JD
Ahmad
Iqbal
I
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002642:Chick Embryo; D005260:Female; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
C497575:Lef1 protein, rat; D051821:Lymphoid Enhancer-Binding Factor 1; D051880:Receptors, Notch; D051153:Wnt Proteins