Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure.
The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. Here, we profile global gene expression during optic fissure closure using laser capture microdissected (LCM) tissue from the margins of the fissure. From these data, we identify a unique role for the C(2)H(2) zinc finger proteins Nlz1 and Nlz2 in normal fissure closure. Gene knockdown of nlz1 and/or nlz2 in zebrafish leads to a failure of the optic fissure to close, a phenotype which closely resembles that seen in human uveal coloboma. We also identify misregulation of pax2 in the developing eye of morphant fish, suggesting that Nlz1 and Nlz2 act upstream of the Pax2 pathway in directing proper closure of the optic fissure.
Brown
Jacob D
JD
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Dutta
Sunit
S
Bharti
Kapil
K
Bonner
Robert F
RF
Munson
Peter J
PJ
Dawid
Igor B
IB
Akhtar
Amana L
AL
Onojafe
Ighovie F
IF
Alur
Ramakrishna P
RP
Gross
Jeffrey M
JM
Hejtmancik
J Fielding
JF
Jiao
Xiaodong
X
Chan
Wai-Yee
WY
Brooks
Brian P
BP
D000818:Animals; D001483:Base Sequence; D003103:Coloboma / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005123:Eye / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051762:PAX2 Transcription Factor / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; D012333:RNA, Messenger; D012097:Repressor Proteins; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish; C492749:znf503 protein, zebrafish; C435747:znf703 protein, zebrafish