TY - JOUR
T1 - Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina
AU - Livne-Bar, Izzy
AU - Pacal, Marek
AU - Cheung, Melissa C.
AU - Hankin, Mark
AU - Trogadis, Judy
AU - Chen, Danian
AU - Dorval, Kimberley M.
AU - Bremner, Rod
PY - 2006/3/28
Y1 - 2006/3/28
N2 - In the Chx10-null ocular retardation (orJ) 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 orJ retina, only a small fraction of cells expressing mutated Chx10 mRNA were rods, but this fraction increased after p27Kip1 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.
AB - In the Chx10-null ocular retardation (orJ) 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 orJ retina, only a small fraction of cells expressing mutated Chx10 mRNA were rods, but this fraction increased after p27Kip1 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.
KW - CVC domain
KW - Homeobox
KW - Homeodomain
KW - Short-hairpin RNA
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U2 - 10.1073/pnas.0600083103
DO - 10.1073/pnas.0600083103
M3 - Article
C2 - 16547132
AN - SCOPUS:33645518611
SN - 0027-8424
VL - 103
SP - 4988
EP - 4993
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -