Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina.
In the Chx10-null ocular retardation (or(J)) mouse, retinal progenitor cell (RPC) proliferation is impaired, and bipolar neurons, a late born cell type, fail to differentiate. It is unclear whether Chx10 is required to maintain proliferation throughout retinogenesis or whether the bipolar cell defect is an indirect effect of growth arrest. We show that Chx10 is dispensable for late-stage RPC proliferation but is essential to promote bipolar cell genesis in place of rods. Ectopic Chx10 expression drove bipolar instead of rod cell differentiation without affecting division. Converting Chx10 to an activator impaired bipolar cell differentiation, implying that repression is important for Chx10 activity. In the Chx10 null or(J) retina, only a small fraction of cells expressing mutated Chx10 mRNA were rods, but this fraction increased after p27(Kip1) inactivation, which partially rescues proliferation. Most significantly, acute Chx10 knockdown in the postnatal retina promoted rods in place of bipolar neurons without affecting division. Thus, Chx10 directly controls bipolar cell genesis by inhibiting rod differentiation independent of its temporally limited early effect on RPC proliferation.
Livne-Bar
Izzy
I
Toronto Western Research Institute, University Health Network.
Pacal
Marek
M
Cheung
Melissa C
MC
Hankin
Mark
M
Trogadis
Judy
J
Chen
Danian
D
Dorval
Kimberley M
KM
Bremner
Rod
R
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010786:Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C088975:Vsx2 protein, mouse