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. 2024 Mar 14;15(3):363.
doi: 10.3390/genes15030363.

The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development

Judith Habicher  1 , Ilaria Sanvido  1 , Anja Bühler  1   2 , Samuele Sartori  1 , Giovanni Piccoli  1 , Matthias Carl  1
Affiliations

The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development

Judith Habicher et al. Genes (Basel). .

Abstract

The immunoglobulin LAMP/OBCAM/NTM (IgLON) family of cell adhesion molecules comprises five members known for their involvement in establishing neural circuit connectivity, fine-tuning, and maintenance. Mutations in IgLON genes result in alterations in these processes and can lead to neuropsychiatric disorders. The two IgLON family members NEGR1 and OPCML share common links with several of them, such as schizophrenia, autism, and major depressive disorder. However, the onset and the underlying molecular mechanisms have remained largely unresolved, hampering progress in developing therapies. NEGR1 and OPCML are evolutionarily conserved in teleosts like the zebrafish (Danio rerio), which is excellently suited for disease modelling and large-scale screening for disease-ameliorating compounds. To explore the potential applicability of zebrafish for extending our knowledge on NEGR1- and OPCML-linked disorders and to develop new therapeutic strategies, we investigated the spatio-temporal expression of the two genes during early stages of development. negr1 and opcml are expressed maternally and subsequently in partially distinct domains of conserved brain regions. Other areas of expression in zebrafish have not been reported in mammals to date. Our results indicate that NEGR1 and OPCML may play roles in neural circuit development and function at stages earlier than previously anticipated. A detailed functional analysis of the two genes based on our findings could contribute to understanding the mechanistic basis of related psychiatric disorders.

Keywords: IgLON; brain; negr1; neuropsychiatric disorder; opcml; zebrafish development.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
negr1 and opcml expression at early developmental stages. 16-cell stage zebrafish embryos expressing negr1 (A) and opcml (B); sense probe stains are shown in the insets. (C,D) show lateral views of 12 hpf old embryos. negr1 is expressed in the midbrain and the otic placodes (C), while opcml exhibits ubiquitous expression (D). RT-PCR corroborates the presence of negr1 and opcml transcripts at the 16-cell stage (E). MB, midbrain; OP, otic placodes.
Figure 2
Figure 2
Expression patterns of negr1 and opcml at 24 hpf and 48 hpf. Dorsal (A,B,E,F) and lateral (C,D,G,H) views of the head region of zebrafish embryos at stages indicated. Insets show the pineal gland (A,B), the otic vesicle (C,D), the spinal cord (upper inset in C), and a frontal view (E). HB, hindbrain; OB, olfactory bulb; OP, olfactory placode; OV, otic vesicle; PTh, pre-thalamus; P, pineal gland; SC, spinal cord; V, ventral telencephalon.
Figure 3
Figure 3
Expression patterns of negr1 and opcml at 96 hpf and 120 hpf. Dorsal (A,B,E,F) and lateral (C,D) views of zebrafish larvae focussed on the head at stages indicated. Transversal sections were carried out at the level of the pineal organ (G,H). Ce, cerebellum (inset in (A,B)); Hb, habenula; INL, inner nuclear layer; OB, olfactory bulb; Pa, pallium; P, pineal gland; OT, optic tectum.
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