Zebrafish rx3 and mab21l2 are required during eye morphogenesis
- Kennedy, B.N., Stearns, G.W., Smyth, V.A., Ramamurthy, V., van Eeden, F., Ankoudinova, I., Raible, D., Hurley, J.B., and Brockerhoff, S.E.
- Developmental Biology 270(2): 336-349 (Journal)
- Registered Authors
- Brockerhoff, Susan, Hurley, James B., Kennedy, Breandan N., Raible, David, van Eeden, Freek
- MeSH Terms
- Chromosome Mapping
- Crosses, Genetic
- DNA, Complementary/genetics
- Gene Expression Regulation, Developmental*
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- In Situ Hybridization
- In Situ Nick-End Labeling
- Polymorphism, Single-Stranded Conformational
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Analysis, DNA
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish Proteins
- 15183718 Full text @ Dev. Biol.
Kennedy, B.N., Stearns, G.W., Smyth, V.A., Ramamurthy, V., van Eeden, F., Ankoudinova, I., Raible, D., Hurley, J.B., and Brockerhoff, S.E. (2004) Zebrafish rx3 and mab21l2 are required during eye morphogenesis. Developmental Biology. 270(2):336-349.
Two alleles of an eyeless mutant, chokh (chk), were identified in ongoing zebrafish F(3) mutagenesis screens. Morphologically, chk mutants can be identified at 15 h post-fertilization by the failure of optic primordia to evaginate from the forebrain. The chk phenotype appears specific, as marker genes in the forebrain, midbrain, and pineal are expressed in normal temporal, spatial, and circadian patterns. Sequence analysis of the chk alleles revealed nonsense or missense mutations in the rx3 homeobox. Rx genes encode paired-type homeodomain transcription factors known to be key regulators of eye development in mouse, medaka, Xenopus, and zebrafish. To uncover novel Rx targets, we analyzed the expression of multiple eye development genes in chk. We find that expression of mab21l2, mab21l1 and rx2 are specifically absent in the eye field of chk embryos. Knockdown of Mab21l2 by antisense morpholino microinjections partially phenocopies the rx3 mutation, leading to microphthalmia, incomplete eye maturation, and dramatic increases in apoptotic eye progenitors. We propose that mab21l2 is an early downstream effector of rx3 and is critical for survival of eye progenitors.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes