Expression of Three Gene Families Encoding Cell–Cell Communication Molecules in the Prepubertal Nonhuman Primate Hypothalamus

Abstract

Transsynaptic and glial-neuronal communication are important components of the mechanism underlying the pubertal activation of luteinizing hormone-releasing hormone (LHRH) secretion. The molecules required for the architectural organization of these cell-cell interactions have not been identified. We now show that the hypothalamus of the prepubertal female rhesus monkey expresses a multiplicity of genes encoding three families of adhesion/signalling proteins involved in the structural definition of both neurone-to-neurone and bi-directional neurone-glia communication. These include the neurexin/neuroligin (NRX/NRL) and protocadherin-alpha (PCDHalpha) families of synaptic specifiers/adhesion molecules, and key components of the contactin-dependent neuronal-glial adhesiveness complex, including contactin/F3 itself, the contactin-associated protein-1 (CASPR1), and the glial receptor protein tyrosine phosphatase beta. Prominently expressed among members of the NRX family is the neurexin isoform involved in the specification of glutamatergic synapses. Although NRXs, PCDHalphas and CASPR1 transcripts are mostly detected in neurones, the topography of expression appears different. NRX1 mRNA-containing neurones are scattered throughout the hypothalamus, PCDHalpha mRNA transcripts appear more abundant in neurones of the arcuate nucleus and periventricular region, and neurones positive for CASPR1 mRNA exhibit a particularly striking distribution pattern that delineates the hypothalamus. Examination of LHRH neurones, using the LHRH-secreting cell line GT1-7, showed that these cells contain transcripts encoding NRXs and one of their ligands (NRL1), at least one PCDHalpha (CNR-8/PCDHalpha10), and the CASPR1/contactin complex. The results indicate that the prepubertal female monkey hypothalamus contains a plethora of adhesion/signalling molecules with different but complementary functions, and that an LHRH neuronal cell line expresses key components of this structural complex. The presence of such cell-cell communication machinery in the neuroendocrine brain suggests an integrated participation of their individual components in the central control of female sexual development.