NELL2, a neuron-specific EGF-like protein, is selectively expressed in glutamatergic neurons and contributes to the glutamatergic control of GnRH neurons at puberty

Chang Man Ha, Jungil Choi, Eun Jung Choi, Maria E. Costa, Byung Ju Lee, Sergio Ojeda

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    NELL2, a protein containing EGF-like repeats, is almost exclusively expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. NELL2 was previously found to be a secreted protein that functions during embryonic development as a neuronal differentiation and survival factor. We now show that the Nell2 gene is selectively expressed in the two major subtypes of glutamatergic neurons described in the postnatal brain: those containing the vesicular glutamate transporter 1 and those expressing vesicular glutamate transporter 2. No Nell2 mRNA is detected in GABAergic neurons. Likewise, GnRH neurons are devoid of NELL2. During prepubertal development of the female rat, Nell2 mRNA abundance increases selectively in the medial basal hypothalamus, reaching maximal values at the end of the juvenile period, to decline at the time of puberty to intermediate levels. Similar, but less pronounced changes are observed in the preoptic area, but they are absent in the cerebral cortex. A well-established glutamatergic function in the neuroendocrine brain is to enhance release of GnRH, the neurohormone controlling sexual development and the time of puberty. In vivo disruption of NELL2 synthesis via intraventricular administration of antisense oligodeoxynucleotides reduced GnRH release from the medial basal hypothalamus and delayed the initiation of female puberty. These results identify NELL2 as a new component of glutamatergic neurons and provide evidence for its physiological involvement in a major, glutamate-dependent, process of neuroendocrine regulation.

    Original languageEnglish (US)
    Pages (from-to)199-211
    Number of pages13
    JournalNeuroendocrinology
    Volume88
    Issue number3
    DOIs
    StatePublished - Oct 2008

    Fingerprint

    Puberty
    Epidermal Growth Factor
    Gonadotropin-Releasing Hormone
    Middle Hypothalamus
    Neurons
    Vesicular Glutamate Transport Protein 1
    Vesicular Glutamate Transport Protein 2
    Brain
    GABAergic Neurons
    Messenger RNA
    Sexual Development
    Proteins
    Preoptic Area
    Oligodeoxyribonucleotides
    Cerebral Cortex
    Nervous System
    Embryonic Development
    Neurotransmitter Agents
    Glutamic Acid
    Genes

    Keywords

    • Ca-binding protein
    • Epidermal growth factor-like repeat domains
    • Female puberty
    • Glutamate release
    • Synaptophysin

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism
    • Endocrine and Autonomic Systems
    • Cellular and Molecular Neuroscience

    Cite this

    NELL2, a neuron-specific EGF-like protein, is selectively expressed in glutamatergic neurons and contributes to the glutamatergic control of GnRH neurons at puberty. / Ha, Chang Man; Choi, Jungil; Choi, Eun Jung; Costa, Maria E.; Lee, Byung Ju; Ojeda, Sergio.

    In: Neuroendocrinology, Vol. 88, No. 3, 10.2008, p. 199-211.

    Research output: Contribution to journalArticle

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