Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei

Abstract

Transcription factors of the Nuclear Factor I (Nfi) family are important for the development of specific neuronal and glial populations in the nervous system. One such population, the neurons of the basilar pontine nuclei, expresses high levels of Nfi proteins, and the pontine nuclei are greatly reduced in mice lacking a functional Nfib gene. Pontine neurons, along with other precerebellar neurons that populate the hindbrain, arise from precursors in the lower rhombic lip and migrate anteroventrally to reach their final location. Using immunohistochemistry, we find that NFI-B expression is specific for mossy fiber populations of the precerebellar system. Analysis of the Nfib ؊/؊ hindbrain indicates that the development of the basilar pontine nuclei is delayed, with pontine neurons migrating 1-2 days later than in control animals, and that significantly fewer pontine neurons are produced. While the mossy fiber nuclei of the caudal medulla do form, they also exhibit a developmental delay. Indexing terms: precerebellar; mossy fiber; cell migration; neurogenesis; hindbrain The mature brain is composed of many subclasses of neurons and glia, each of which acquires a unique identity during development. Such identity is conferred by transcription factors that work alone or in combination to determine cell fate. One set of transcription factors that is critical for the development of specific subpopulations of both neurons and glia in the nervous system are the Nuclear Factor I (Nfi) transcription factors, a family consisting of Nfia, Nfib, Nfic, and Nfix (for a general review, see Gronostajski, 2000). Additional diversity in this set of factors is generated by alternative splicing, resulting in several possible isoforms for each protein.

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

“…One genetic candidate in neural progenitor cell maintenance is NFIB, a member of the Nuclear Factor One (NFI) family of transcription factors that is essential for normal brain development. 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).…”

Nuclear Factor I Genes Regulate Neuronal Migration

“…For instance, mice lacking this transcription factor display enlarged lateral ventricles, dysgenesis of the corpus callosum and failure of glial maturation at the telencephalic midline [26], while also exhibiting cerebellar and hippocampal defects [28,34]. Development of the pons within Nfib mutants is also abnormal, with development of neurons within the pontine nuclei occurring substantially later than in control mice [35]. …”

Discovering sparse transcription factor codes for cell states and state transitions during development

“…The $c_5-c_6$ branch is inferred from transition genes including PAX3, CRX, SOX11, EBF2, FOXP4, ASCL1, FOXO3 , and SIX3 which have strong expression in developing dopaminergic and gabaergic neurons of the midbrain (Agoston et al, 2012; Erickson et al, 2010; Pino et al, 2014; Yang et al, 2015; Yin et al, 2009; Zhang et al, 2002). Transition genes in the $c_5-c_7$ branch include ARGFX, DUXA, HES1, NFIB, PPARA, SOX2, SOX7 , and SOX9 , which are known to be associated with the medulla oblongata region of the hindbrain (Fawcett and Klymkowsky, 2004; Kameda et al, 2011; Kumbasar et al, 2009; Madissoon et al, 2016; Matsui et al, 2000; Stolt et al, 2003). …”