Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages

Quiñones, Herson I.; Savage, Trisha K.; Battiste, James; Johnson, Jane E.

doi:10.1016/j.ydbio.2010.02.012

Cited by 40 publications

(43 citation statements)

References 55 publications

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“…To determine whether Shh produced by the spiral ganglion affects cochlear development, we generated ganglionspecific knockouts using three different cre strains: Foxg1 Cre , Ngn1 Cre , and Ngn1 CreERT2 (16)(17)(18). Neurogenin1 (Ngn1) expression is initiated in neuroblasts of the CVG before their delamination from the otic epithelium (19).…”

Section: Resultsmentioning

confidence: 99%

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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.

111

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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...

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Section: Resultsmentioning

confidence: 99%

“…Foxg1 is expressed in the otocyst and CVG (16). Based on published cre reporter activities, all three cre strains should ablate Shh expression in the CVG (16)(17)(18) while sparing its expression in the notochord and floor plate, two sources of Shh thought to be required for specification of cochlear identity (10,11).…”

Section: Resultsmentioning

confidence: 99%

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.

111

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show abstract

“…and M.G., unpublished), Ai14 (R26 floxstop-tdTomato ) (Madisen et al, 2010), Foxd3 flox/flox (Teng et al, 2008), Oc1 -/-;Oc2 lacZ/lacZ (Clotman et al, 2005), Nes::Cre (Tronche et al, 1999), Ngn1::Cre (Quinones et al, 2010), ZnG (Zhang et al, 2008) and MafB GFP (Blanchi et al, 2003). PCR genotyping was undertaken with allele-specific primers for each strain.…”

Section: Micementioning

confidence: 99%

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program

et al. 2012

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SUMMARYThe spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants.

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“…The ability of genomic constructs to drive tissue-and time-specific expression, unlike cDNA and mini-genes, has made BAC transgenics an additional tool to knockout transgenics for the identification of potential regulatory elements within the locus of a gene. For instance, an enhancer within the locus of the tyrosinase-related family (Tyrp1) gene (Murisier et al, 2006) and a region responsible for tissue-specific expression within the locus of the Neurogenin1 gene (Quiñones et al, 2010) have been discovered in transgenic mice generated with BACs.…”

Section: Advantages Of Use Of Genomic Constructs In Gene Therapymentioning

confidence: 99%

Non-Viral Gene Therapy Vectors Carrying Genomic Constructs

Kotzamanis¹,

Abdulrazzak²,

Kotsinas³

et al. 2011

Non-Viral Gene Therapy

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Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages

Cited by 40 publications

References 55 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

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program

Non-Viral Gene Therapy Vectors Carrying Genomic Constructs

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