Olfactomedin-2 mediates development of the anterior central nervous system and head structures in zebrafish

Abstract

Olfactomedins comprise a diverse family of secreted glycoproteins, which includes noelin, tiarin, pancortin and gliomedin, implicated in development of the nervous system, and the glaucoma-associated protein myocilin. Here we show in zebrafish that olfactomedin-2 (OM2) is a developmentally regulated gene, and that knockdown of protein expression by morpholino antisense oligonucleotides leads to perturbations of nervous system development. Interference with OM2 expression results in impaired development of branchiomotor neurons, specific disruption of the late phase branchiomotor axon guidance, and affects development of the caudal pharyngeal arches, olfactory pits, eyes and optic tectum. Effects of OM2 knockdown on eye development are likely associated with Pax6 signaling in developing eyes, as Pax6.1 and Pax6.2 mRNA expression patterns are altered in the eyes of OM2 morphants. The specific absence of most cartilaginous structures in the pharyngeal arches indicates that the observed craniofacial phenotypes may be due to perturbed differentiation of cranial neural crest cells. Our studies show that this member of the olfactomedin protein family is an important regulator of development of the anterior nervous system.

Olfactomedin 2: Expression in the Eye and Interaction with Other Olfactomedin Domain–Containing Proteins

“…In the developing zebrafish eye, Olfm2 was detected, not only in the retinal ganglion cell layer but also in the inner nuclear layer. 31 Similarly, Olfm3 which is most closely related to Olfm2, is expressed in both retinal ganglion and inner nuclear layers of adult rat retina. 19 It is interesting to note that another family member, Olfm4, is preferentially expressed in adult mouse Müller glial cells.…”

“…31 In zebrafish, Olfm2, similar to Olfm1a and -1b genes, is preferentially expressed in the developing central nervous system, as well as in neural-crest-derived structures. 23,31 Here, we studied the expression pattern of the Olfm2 gene in mammalian brain and eye and compared it with the expression patterns of the Olfm1 and -3 genes. Olfm2 showed the most dynamic pattern of expression compared with Olfm1 and -3 in the course of mouse eye and brain development, as judged by real-time PCR (Figs.…”

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon)

“…OLFM1 and OLFM2 are preferentially expressed in the developing retinal ganglion cells [16] in rat and mouse. In zebrafish eye OLFM2 was detected in the retinal ganglion cell layer and the inner nuclear layer [28]. OLFML2 in humans was found by RT-PCR in corneal endothelium, uvea, lens and retina-RPE.…”

Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice

“…It should be mentioned that knockdown of olfm2 expression in zebrafish using morpholino oligonucleotides leads to more pronounced defects than Olfm2 null mutation in mice. Interference with olfm2 expression resulted in impaired development of branchiomotor neurons, specific disruption of the late phase branchiomotor axon guidance, and affected development of the caudal pharyngeal arches, olfactory pits, eyes and optic tectum (Lee et al, 2008). These discrepancies in morphological defects between mice and zebrafish could be explained by species differences.…”

“…Olfm2 together with olfactomedin 1 (Olfm1) and olfactomedin 3 (Olfm3) forms subfamily I. Genes encoding Olfm1-3 are preferentially expressed in the neuronal tissues during development and in adults (Danielson et al, 1994, Nagano et al, 2000, Torrado et al, 2002, Lee et al, 2008, Nakaya et al, 2008, Nakaya et al, 2012). Olfm1-3 show about 60% identity in the amino acid sequences and are highly conserved in evolution (Tomarev and Nakaya, 2009).…”