NMDA receptor activation in differentiating cerebellar cell cultures regulates the expression of a new POU gene, Cns-1

Abstract

POU/homeobox genes encode transcription regulatory proteins that are important in defining cellular phenotypes. Expression of these genes may be critical for to the regulation of CNS cellular differentiation. We have identified a cDNA corresponding to a new member of the POU/homeobox gene family. Expression of RNA encoded by this new gene occurs predominantly in the CNS. Thus, this new gene was designated Cns- 1. Cns-1 transcripts are expressed in differentiating cells cultured from the early postnatal cerebellum. Treatment of these cultured cells with NMDA results in an increase in the level of Cns-1 RNA. This increase is blocked by simultaneous treatment with the specific NMDA receptor antagonist amino-5-phosphonovaleric acid. Continued activation of the NMDA receptor allows maintenance of this new steady state level of Cns-1 mRNA for at least 5 d in these cultured cells. A transcription runoff assay suggests that this increase in the level of RNA is due, at least in part, to an increase in transcription from the Cns-1 gene. The NMDA-induced increase in Cns-1 mRNA was reduced by pretreatment with calcium chelators EGTA or 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′- tetraacetic acid (BAPTA) tetrakis(acetoxymethyl). These studies suggest that specific activation of the NMDA receptor in cultures of differentiating cerebellar cells increases Cns-1 gene expression and that calcium entry through the NMDA channel may be required for this response. This change in Cns-1 expression may modify phenotypic characteristics of these cultured cells.

Model of forebrain regionalization based on spatiotemporal patterns of POU‐III homeobox gene expression, birthdates, and morphological features

“…It is likely that signal transduction pathways functionally modulate POU-111 factors in response to the physiological state of the developing and mature nervous system. In agreement with the model is the report that a POU gene, Cns-1, can be influenced by specific N-methyl-D-aspartate (NMDA) receptor activation in cultures of differentiating cerebellar cells (Bulleit et al, 1994), suggesting that the arrival of axonal inputs or certain kinds of synaptic activity may contribute to POU transcription factor expression regulation through altered calcium levels.…”

Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family

“…Another candidate gene is a new POU gene, CNS-1. CNS-1 is predominantly expressed in the central nervous system (Bulleit et al, 1994), but its precise chromosome location is not yet known. Treatment with n-methyl-d-aspartate (NMDA) resulted in an increase in the level of CNS-1 RNA.…”

POU domain family values: flexibility, partnerships, and developmental codes.

“…I-POU Brn-3.0/Brn-3a (RDC-i, POU4F1) oogenesis and early embryo both: gap-like pattern in early embryo; peripheral sensory organs; neuroectoderm, neuroblasts; ectoderm; Pdm-1 only--throughout wing primordium B cells; alternative splice forms in nervous system skin (keratinocytes) all levels of CNS in embryo and adult--more restricted in adult; intestine, kidney overlapping expression in embryonic and adult nervous system; pronephric Wolffian duct all levels of CNS in embryo and adult--more restricted expression in adult [Z] all levels of CNS in embryo and adult [Z] all levels of CNS in embryo and adult [X l not described [M] all SpOct (Char et al 1993);zp-12, zp23, zp47 (Spaniol et al 1996);CEH-6 (Burglin et al 1989); RPF-1 ; pou[c] (Johansen et al 1993);Brn-5 (Andersen et al 1993c); emb (Okamoto et al, 1993); mPOU (Wey et al 1994); Cns-1 (Bulleit et al 1994). UTargeted disruption of the CD3 n locus affects Oct-1 transcription, which is encoded on the opposite strand.…”