<i>Foxg1</i> is required for proper separation and formation of sensory cristae during inner ear development

Hwang, Chan Ho; Simeone, Antonio; Lai, Eseng; Wu, Doris K.

doi:10.1002/dvdy.22111

Cited by 57 publications

(56 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the Foxg1 null cochlea, although shortened as well (23,24), did not display a similar reverse gradient or up-regulation of Atoh1 expression (Fig. S7).…”

Section: Discussionmentioning

confidence: 88%

Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

Bok

Zenczak

Hwang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

111

View full text Add to dashboard Cite

Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissuespecific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.morphogenesis | Atoh1 | tonotopy T he mammalian cochlea, a coiled sensory end organ of hearing, contains a specialized mechanosensory epithelium (organ of Corti) consisting of hair cells (HCs) and nonsensory supporting cells. Sound frequency discrimination in mammals begins in the cochlea with a frequency-place code, such that specific frequencies elicit maximal responses of the organ of Corti at different points along its longitudinal (basal-apical) axis, a phenomenon known as tonotopy. Many structural and molecular features of the mature organ of Corti that vary along the longitudinal (tonotopic) axis, including stiffness of the basilar membrane and size and shape of the sensory HCs and their associated stereocilia (1, 2), have been implicated as contributing factors in frequency discrimination. The developmental bases of tonotopy remain obscure, however (3).A possible developmental influence on tonotopy is the wellcharacterized dynamic of apical (low-frequency sensing) precursors exiting early from the cell cycle, evident at embryonic day (E) 12.5 in mice, followed by a wave-like spread of terminal mitosis toward the base (high-frequency sensing), with cells completing cell cycle exit (CCE) by E14.5 (Fig. 1A) (4, 5). In contrast, early markers of HC differentiation, such as atonal homolog 1 (Atoh1), first appear at the midbase at E13.5 and spread bidirectionally along the developing organ of Corti (Fig. 1A) (6). Consequently, apically located HC precursors remain in a postmitotic, undifferentiated state for a longer period than their more basal counterparts. This unusual pattern of cellular regulation is in stark contrast to the neural precursors in the cortex and retina, in which each neuronal subtype has a specific timing of terminal mitosis, followed closely by its differentiation (7,8).Gradients of secreted molecules are important for patterning and cell fate specification during embryogenesis. Although t...

show abstract

“…Furthermore, the Foxg1 null cochlea, although shortened as well (23,24), did not display a similar reverse gradient or up-regulation of Atoh1 expression (Fig. S7).…”

Section: Discussionmentioning

confidence: 88%

Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

Bok

Zenczak

Hwang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

111

View full text Add to dashboard Cite

show abstract

“…Fgf10 has been shown to enhance the Foxg1-null inner ear phenotype (Pauley et al, 2006); however, it is unlikely that the Chd7 conditional null inner ear defects reported here can be attributed to the presence of Foxg1-Cre. Foxg1 +/-mice are reported to have no inner ear defects, and neurosensory domain specification is unaltered in Foxg1 -/-mice (Hwang et al, 2009;Pauley et al, 2006). Interestingly, OTX2 is implicated in mouse cochlear morphogenesis (Morsli et al, 1999).…”

Section: Research Articlementioning

confidence: 99%

The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear

et al. 2010

View full text Add to dashboard Cite

SUMMARYInner ear neurogenesis is positively regulated by the pro-neural bHLH transcription factors Ngn1 and NeuroD, but the factors that act upstream of this regulation are not well understood. Recent evidence in mouse and Drosophila suggests that neural development depends on proper chromatin remodeling, both for maintenance of neural stem cells and for proper neuronal differentiation. Here, we show that CHD7, an ATP-dependent chromatin remodeling enzyme mutated in human CHARGE syndrome, is necessary for proliferation of inner ear neuroblasts and inner ear morphogenesis. Conditional deletion of Chd7 in the developing otocyst using Foxg1-Cre resulted in cochlear hypoplasia and complete absence of the semicircular canals and cristae. Conditional knockout and null otocysts also had reductions in vestibulo-cochlear ganglion size and neuron number in combination with reduced expression of Ngn1, Otx2 and Fgf10, concurrent with expansion of the neural fate suppressor Tbx1 and reduced cellular proliferation. Heterozygosity for Chd7 mutations had no major effects on expression of otic patterning genes or on cell survival, but resulted in decreased proliferation within the neurogenic domain. These data indicate that epigenetic regulation of gene expression by CHD7 must be tightly coordinated for proper development of inner ear neuroblasts.

show abstract

“…Foxg1 encodes for a winged-helix TF expressed by rostral CNS and sense organs, crucial for their morphogenesis [43][44][45][46][47][48]. It is involved in several aspects of telencephalic development, including specification of the telencephalic field [49], specification of basal ganglia, paleo-and neo-cortex [48,50,51], and cortical laminar specification [21,52].…”

Section: Introductionmentioning

confidence: 99%

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

et al. 2010

View full text Add to dashboard Cite

Neural stem cells (NSCs) give rise to all cell types forming the cortex: neurons, astrocytes, and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors in a highly regulated way. This process is mastered by large sets of genes, among which some implicated in central nervous system pattern formation. The aim of this study was to disentangle the kinetic and histogenetic roles exerted by two of these genes, Emx2 and Foxg1, in cortico-cerebral precursors. For this purpose, we set up a new integrated in vitro assay design. Embryonic cortical progenitors were transduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs and neuronal progenitors. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins driven by cell type-specific promoters and by cell type-specific antibodies and were scored via multiplex cytofluorometry and immunocytofluorescence. A detailed picture of Emx2 and Foxg1 activities in cortico-cerebral histogenesis resulted from this study. Unexpectedly, we found that both genes inhibit gliogenesis and promote neuronogenesis, through distinct mechanisms, and Foxg1 also dramatically stimulates neurite outgrowth. Remarkably, such activities, alone or combined, may be exploited to ameliorate the neuronal output obtainable from neural cultures, for purposes of cell-based brain repair. STEM CELLS

show abstract

Foxg1 is required for proper separation and formation of sensory cristae during inner ear development

Cited by 57 publications

References 38 publications

Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

Contact Info

Product

Resources

About