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Abstract
<p class="first" id="P1">Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian
homolog of the
<i>Aspergillus nidulans</i> nuclear distribution molecule NudE. NDEL1 plays a critical
role in neuronal migration,
neurite outgrowth and neuronal positioning during brain development; however within
the adult central nervous system, limited information is available regarding NDEL1
expression and functions. Here, the goal was to examine inducible NDEL1 expression
in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain,
including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression
was principally localized to perikarya. Using a combination of immunolabeling and
RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression
within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm.
Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding
protein (CREB) binding site within the CpG island proximal to the
<i>NDEL1</i> gene, and
<i>in vivo</i> transgenic repression of CREB led to a marked downregulation of seizure-evoked
NDEL1
expression. Together these data indicate that NDEL1 is inducibly expressed in the
adult nervous system, and that signaling via the CREB/CRE transcriptional pathway
is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth
during development raises the interesting prospect that inducible NDEL1 in the mature
nervous system could contribute to the well-characterized structural and functional
plasticity resulting from repetitive seizure activity.
</p>