Nuclear Factor One Transcription Factors in CNS Development

Abstract

Transcription factors are key regulators of central nervous system (CNS) development and brain function. Research in this area has now uncovered a new key player-the nuclear factor one (NFI) gene family. It has been almost a decade since the phenotype of the null mouse mutant for the nuclear factor one A transcription factor was reported. Nfia null mice display a striking brain phenotype including agenesis of the corpus callosum and malformation of midline glial populations needed to guide axons of the corpus callosum across the midline of the developing brain. Besides NFIA, there are three other NFI family members in vertebrates: NFIB, NFIC, and NFIX. Since generation of the Nfia knockout (KO) mice, KO mice for all other family members have been generated, and defects in one or more organ systems have been identified for all four NFI family members (collectively referred to as NFI here). Like the Nfia KO mice, the Nfib and Nfix KO mice also display a brain phenotype, with the Nfib KO forebrain phenotype being remarkably similar to that of Nfia. Over the past few years, studies have highlighted NFI as a key payer in a variety of CNS processes including axonal outgrowth and guidance and glial and neuronal cell differentiation. Here, we discuss the importance and role of NFI in these processes in the context of several CNS systems including the neocortex, hippocampus, cerebellum, and spinal cord at both cellular and molecular levels.

Nuclear factor one B regulates neural stem cell differentiation and axonal projection of corticofugal neurons

“…Immunohistochemical analysis of E12.5 and E13.5 brains revealed coexpression of NFIB and Ki67, confirming NFIB expression in neural progenitors (Figure 2A, E, P and T) (Plachez et al, 2008;Mason et al, 2009). Starting at E12.5, two major progenitor cell types were present: radial glia and basal progenitors.…”

“…NFIA, another transcription factor in the Nfi gene family, is expressed in proliferative zones and deep layer cortical neurons (Plachez et al, 2008;Mason et al, 2009), but whether NFIA and NFIB are expressed in the same cells is unknown. We observed βGAL and NFIA co-expression in the VZ and layer 6 ( Figure 3G).…”

“…Mice with an NfiB gene mutation (NfiB −/− ) have enlarged lateral ventricles, agenesis of the corpus callosum, defects in the formation of the hippocampus, basilar pons and midline structures and die at birth due to lung defects (Plachez et al, 2008;Kumbasar et al, 2009;Piper et al, 2009). NFIB regulates the migration and axonal projection of cerebellar granule neurons (Wang et al, 2007;Mason et al, 2009;Heng et al, 2012). Furthermore, NFIB is expressed in the proliferative zone and in subcerebral and corticothalamic projection neurons (Plachez et al, 2008;Mason et al, 2009;McKenna et al, 2011), but its role in regulating neural progenitor maintenance and development of these neurons remains to be elucidated.…”

“…NFIB regulates the migration and axonal projection of cerebellar granule neurons (Wang et al, 2007;Mason et al, 2009;Heng et al, 2012). Furthermore, NFIB is expressed in the proliferative zone and in subcerebral and corticothalamic projection neurons (Plachez et al, 2008;Mason et al, 2009;McKenna et al, 2011), but its role in regulating neural progenitor maintenance and development of these neurons remains to be elucidated.…”

Regulatory Factor X Transcription Factors Control Musashi1 Transcription in Mouse Neural Stem/Progenitor Cells

“…The mutation in the NfI binding site in the Msi1-6IE reporter gene also reduced transcriptional activity. NfIa, NfIb, and NfIx are expressed in the developing mouse brain by E15 and E16, and NfIa and NfIb are expressed in the VZ and SVZ [40]. NfI targets the GFAP promoter prior to the induction of astrocyte differentiation in NS/PCs [41,42].…”