Ontogeny and the possible function of a novel epidermal growth factor‐like repeat domain‐containing protein, NELL2, in the rat brain

Abstract

In this study we investigated the mRNA expression of NELL2, a neural tissue-specific epidermal growth factor (EGF)-like repeat domain-containing protein, in the developing and adult rat CNS using in situ hybridization histochemistry and northern blot analysis. The possible candidates that interact with or be regulated by NELL2 were screened with a cDNA expression array in antisense (AS) NELL2 oligodeoxynucleotide (ODN)-injected rat hypothalami. NELL2 mRNA was detected as early as embryonic day 10, and was predominant in the CNS throughout the pre-natal stages. Its expression gradually increased during embryonic development and its strong expression was observed throughout the CNS until embryonic day 20. It was detected in the ventricular zone of the spinal cord, medulla and pons in 12-day-old-embryos, suggesting that NELL2 plays a role in the neurogenesis of these areas. After birth its expression gradually decreased, but high levels of expression could be observed in the tenia tecta, piriform cortex, hippocampus, dentate gyrus, cerebellar cortex, ambiguus nucleus, and inferior olivary nucleus of adult rat brains. The analysis of cDNA expression arrays revealed that the administration of AS NELL2 ODN markedly decreased the expression of several Ca 2+ -binding proteins and those involved in the transport and release of vesicles such as EF-hand Ca 2+ -binding protein p22 and rab7. This finding was confirmed by relative reverse transcription-polymerase chain reaction. The effect of NELL2 on synaptic vesicle content in median eminence (ME) nerve terminals was determined with synaptophysin levels as a marker protein in the AS NELL2 ODN-injected rat. It was significantly decreased by the AS ODN. These data suggest that NELL2 may play an important role in the development of the CNS as well as maintenance of neural functions, by regulating the intracellular machinery involving Ca 2+ signaling, synaptic transport and/or release of vesicles.

Regulation of the Female Rat Estrous Cycle by a Neural Cell-Specific Epidermal Growth Factor-like Repeat Domain Containing Protein, NELL2

“…As a control, a scrambled (SCR) sequence of identical base composition was used (5′-TAT CGC ATG CGG GCC TAT GCG-3′). For the icv injection, the ODNs were diluted to a final concentration of 100 ng/ml in artificial cerebrospinal fluid (ACSF) (Kim et al, 2002). Immediately after OVX surgery, a polyethylene cannula (O.D.…”

“…Because NELL2 is ubiquitously expressed in neurons, it was considered to play general roles in maintaining neuronal functions (Kim et al, 2002;Oyasu et al, 2000). However, we recently found that NELL2 is specifically expressed in glutamatergic neurons, but not in the gonadotropin-releasing hormone (GnRH) neurons of the rat hypothalamus (Ha et al, 2008).…”

Shotgun Proteomics and Network Analysis between Plasma Membrane and Extracellular Matrix Proteins from Rat Olfactory Ensheathing Cells

“…Dihydropyrimidinase-related protein 2 (Dpysl2) beresponse to astrocyte injury and may be involved in reg- lar machinery involving Ca 2+ signaling, synaptic transport, and/or release of vesicle (31). Attractin (Atrn) is more REFERENCES widely expressed throughout the CNS than previously genesis in vitro.…”

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

“…Two human and rat cDNAs were later isolated as NELL1 and NELL2 (nel-like genes), with 50% and 80% homology to nel Luce and Burrows, 1999;Watanabe et al, 1996). Neural tissue-specific expression of NELL2 has been reported in developing and post-natal rats (Kim et al, 2002;Nelson et al, 2004;Oyasu et al, 2000) and humans (Watanabe et al, 1996). NELL2 mRNA is predominantly expressed in the central nervous system throughout the pre-natal stages, and its expression gradually increases during embryonic development.…”

“…NELL2 mRNA is predominantly expressed in the central nervous system throughout the pre-natal stages, and its expression gradually increases during embryonic development. In the adult rat brain, high levels of NELL2 mRNA are detected in the taenia tecta, piriform cortex, hippocampus, dentate gyrus, cerebellar cortex, ambiguous nucleus, and inferior olivary nucleus (Kim et al, 2002;Oyasu et al, 2000). In addition, NELL2 is an estrogen-induced gene in the adult female rat hypothalamus and is involved in the estrogendependent organization of the sexually dimorphic nucleus in the preoptic area (Jeong et al, 2008).…”