TY - JOUR
T1 - Multiple roles for Pax2 in the embryonic mouse eye
AU - Bosze, Bernadett
AU - Suarez-Navarro, Julissa
AU - Soofi, Abdul
AU - Lauderdale, James D.
AU - Dressler, Gregory R.
AU - Brown, Nadean L.
N1 - Funding Information:
This work was supported by the NIH/NEI EY13612 grant to NLB ; NIH/NEI Core Facilities grant P30 EY012576 to UC Davis; Society for Developmental Biology Choose Development! Fellowship to JS-N; the Children’s Glaucoma Foundation, Vision for Tomorrow and University of Georgia, Dept. of Cellular Biology Vision Research Fund to JDL; and NIH/DDK grant DK054740 to GRD. The authors thank Ruth Ashery Padan for alpha-Cre and Pax6 flox mice; Grant Mastick for netrin1 cDNA; Nick Marsh-Armstrong for eGFP cDNA; Kapil Bharti for Vax1 cDNA; Tom Glaser for Raldh3 cDNA and Pax6 triplex PCR advice; Ratheesh Kumar Meleppat and Robert Zawadzki for help with OCT/SLO imaging; Amy Riesenberg and April Bird for technical support, and the UC Davis Eye Development group for insightful discussions. We also thank Anna La Torre and Nick Marsh-Armstrong for critical evaluation of this manuscript.
PY - 2021/4
Y1 - 2021/4
N2 - The vertebrate eye anlage grows out of the brain and folds into bilayered optic cups. The eye is patterned along multiple axes, precisely controlled by genetic programs, to delineate neural retina, pigment epithelium, and optic stalk tissues. Pax genes encode developmental regulators of key morphogenetic events, with Pax2 being essential for interpreting inductive signals, including in the eye. PAX2 mutations cause ocular coloboma, when the ventral optic fissure fails to close. Previous studies established that Pax2 is necessary for fissure closure and to maintain the neural retina -- glial optic stalk boundary. Using a Pax2GFP/+ knock-in allele we discovered that the mutant optic nerve head (ONH) lacks molecular boundaries with the retina and RPE, rendering the ONH larger than normal. This was preceded by ventronasal cup mispatterning, a burst of overproliferation and followed by optic cup apoptosis. Our findings support the hypothesis that ONH cells are tripotential, requiring Pax2 to remain committed to glial fates. This work extends current models of ocular development, contributes to broader understanding of tissue boundary formation and informs the underlying mechanisms of human coloboma.
AB - The vertebrate eye anlage grows out of the brain and folds into bilayered optic cups. The eye is patterned along multiple axes, precisely controlled by genetic programs, to delineate neural retina, pigment epithelium, and optic stalk tissues. Pax genes encode developmental regulators of key morphogenetic events, with Pax2 being essential for interpreting inductive signals, including in the eye. PAX2 mutations cause ocular coloboma, when the ventral optic fissure fails to close. Previous studies established that Pax2 is necessary for fissure closure and to maintain the neural retina -- glial optic stalk boundary. Using a Pax2GFP/+ knock-in allele we discovered that the mutant optic nerve head (ONH) lacks molecular boundaries with the retina and RPE, rendering the ONH larger than normal. This was preceded by ventronasal cup mispatterning, a burst of overproliferation and followed by optic cup apoptosis. Our findings support the hypothesis that ONH cells are tripotential, requiring Pax2 to remain committed to glial fates. This work extends current models of ocular development, contributes to broader understanding of tissue boundary formation and informs the underlying mechanisms of human coloboma.
KW - Coloboma
KW - Foxg1
KW - Optic stalk
KW - Pax2
KW - Pax6
KW - Retina
KW - RPE
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U2 - 10.1016/j.ydbio.2020.12.020
DO - 10.1016/j.ydbio.2020.12.020
M3 - Article
AN - SCOPUS:85099346142
VL - 472
SP - 18
EP - 29
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
ER -