Olfactomedin1 (Olfm1/Noelin/Pancortin) is a secreted glycoprotein belonging to the family of olfactomedin domain-containing proteins. It is implicated in neurogenesis in Xenopus and generation of the neural crest in chicken. We investigate the functions of Olfm1 in zebrafish development. In the course of development, zebrafish Olfm1a and Olfm1b, two orthologs of mouse Olfm1 genes, were expressed in several organs including the developing eye, brain and spinal cord. Injections of morpholino oligonucleotides against Olfm1 (Olfm1-MO) were used to knockdown Olfm1 expression. Olfm1-MO injection caused severe damage to the brain and eyes, accompanied by cell dissociations from the head and the dorsal part of body. In addition, it caused reduced pigmentation, distorted body axis, expanded heart, and shorter body length. The size of the eye was also reduced by the Olfm1-MO injection. The effects of Olfm1-MO on the brain and eyes were partially rescued by the co-injection with mouse Olfm1 RNA.? The eye size reduction may be explained by dramatically reduced expression of microphilia-associated transcription factors (Mitfs) in Olfm1-MO-injected embryos. Axon extensions in the optic nerve, lateral line nerve and the neuronal network inside of the neural tube were significantly delayed or inhibited by the Olfm1-MO injection. These data suggest that zebrafish Olfm1 may affect neuronal and eye development. ? ? In collaboration with Dr. J. Wilting (University of Goettingen, Germany), we studied development of the lymphatic system in chicken using Prox1, as one of the markers of the lymphatic system. Our results provide evidence for a dual origin of the lymphatics from both the veins and scattered mesodermal precursor cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000311-11
Application #
7322215
Study Section
(MMGS)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva et al. (2013) Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice. Exp Neurol 250:205-18
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Nakaya, Naoki; Tomarev, Stanislav (2007) Expression patterns of alternative transcripts of the zebrafish olfactomedin 1 genes. Gene Expr Patterns 7:723-9
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Steffensen, Knut R; Holter, Elin; Bavner, Ann et al. (2004) Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue. EMBO Rep 5:613-9

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