Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium (original) (raw)
Related papers
Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors
Development (Cambridge, England), 1997
The lineage of olfactory neurons has been relatively well characterized at the cellular level, but the genes that regulate the proliferation and differentiation of their progenitors are currently unknown. In this study, we report the isolation of a novel murine gene, Math4C/neurogenin1, which is distantly related to the Drosophila proneural gene atonal. We show that Math4C/neurogenin1 and the basic helix-loop-helix gene Mash1 are expressed in the olfactory epithelium by different dividing progenitor populations, while another basic helix-loop-helix gene, NeuroD, is expressed at the onset of neuronal differentiation. These expression patterns suggest that each gene marks a distinct stage of olfactory neuron progenitor development, in the following sequence: Mash1>Math4C/neurogenin1>NeuroD. We have previously reported that inactivation of Mash1 function leads to a severe reduction in the number of olfactory neurons. We show here that most cells in the olfactory epithelium of Mas...
Progenitor cells of the olfactory receptor neuron lineage
Microscopy Research and Technique, 2002
The olfactory epithelium of the mouse has many properties that make it an ideal system for studying the molecular regulation of neurogenesis. We have used a combination of in vitro and in vivo approaches to identify three distinct stages of neuronal progenitors in the olfactory receptor neuron lineage. The neuronal stem cell, which is ultimately responsible for continual neuron renewal in this system, gives rise to a transit amplifying progenitor identified by its expression of a transcription factor, MASH1. The MASH1-expressing progenitor gives rise to a second transit amplifying progenitor, the Immediate Neuronal Precursor, which is distinct from the stem cell and MASH1expressing progenitor, and gives rise quantitatively to olfactory receptor neurons. Regulation of progenitor cell proliferation and differentiation occurs at each of these three cell stages, and growth factors of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) families appear to play particularly important roles in these processes. Analyses of the actions of FGFs and BMPs reveal that negative signaling plays at least as important a role as positive signaling in the regulation of olfactory neurogenesis.
Ciba Foundation symposium, 1991
We have developed an in vitro system for studying molecular events regulating neurogenesis in the mouse olfactory epithelium (OE). Our observations suggest that two types of neuronal precursor may be involved: (1) a transiently existing, immediate neuronal precursor (INP), which generates two postmitotic daughter neurons; and (2) a neuroepithelial stem cell, which may be the basal cell (or some subclass of basal cell) of the OE, and is presumed to be the progenitor of the INP. Using antibody markers that distinguish basal cells and postmitotic receptor neurons in vitro and in vivo, we have shown that neurogenesis occurs early on in OE cultures, but then ceases because INPs divide only once to generate postmitotic neurons and no new INPs are produced by basal cells. To determine whether the basal cell-to-INP transition, or proliferation and neuronal differentiation of the INP, are regulated by crucial growth factors or cellular interactions, we are testing various polypeptide growth ...
Morphogenesis is transcriptionally coupled to neurogenesis during olfactory placode development
2019
Morphogenesis of sense organs occurs concomitantly with the differentiation of sensory cells and neurons necessary for their function. While our understanding of the mechanisms controlling morphogenesis and neurogenesis has grown, how they are coordinated remains relatively unknown. The earliest wave of neurogenesis in the zebrafish olfactory placode requires the bHLH proneural transcription factor Neurogenin1 (Neurog1). To address whether Neurog1 couples neurogenesis and morphogenesis in this system, we analyzed the morphogenetic behavior of early olfactory neural progenitors. Our results indicate that the oriented movements of these progenitors are disrupted in neurog1 mutants. Morphogenesis is similarly affected by mutations in the chemokine receptor, cxcr4b, making it a potential Neurog1 target gene. We find that Neurog1 directly regulates cxcr4b through an E-boxes cluster located just upstream of the cxcr4b transcription start site. Our results suggest that proneural transcript...
Development (Cambridge, England), 2002
bHLH transcription factors are expressed sequentially during the development of neural lineages, suggesting that they operate in genetic cascades. In the olfactory epithelium, the proneural genes Mash1 and neurogenin1 are expressed at distinct steps in the same olfactory sensory neuron lineage. Here, we show by loss-of-function analysis that both genes are required for the generation of olfactory sensory neurons. However, their mutant phenotypes are strikingly different, indicating that they have divergent functions. In Mash1 null mutant mice, olfactory progenitors are not produced and the Notch signalling pathway is not activated, establishing Mash1 as a determination gene for olfactory sensory neurons. In neurogenin1 null mutant mice, olfactory progenitors are generated but they express only a subset of their normal repertoire of regulatory molecules and their differentiation is blocked. Thus neurogenin1 is required for the activation of one of several parallel genetic programs fu...
NeuroD1 induces terminal neuronal differentiation in olfactory neurogenesis
Proceedings of the National Academy of Sciences, 2010
After their generation and specification in periventricular regions, neuronal precursors maintain an immature and migratory state until their arrival in the respective target structures. Only here are terminal differentiation and synaptic integration induced. Although the molecular control of neuronal specification has started to be elucidated, little is known about the factors that control the latest maturation steps. We aimed at identifying factors that induce terminal differentiation during postnatal and adult neurogenesis, thereby focusing on the generation of periglomerular interneurons in the olfactory bulb. We isolated neuronal precursors and mature neurons from the periglomerular neuron lineage and analyzed their gene expression by microarray. We found that expression of the bHLH transcription factor NeuroD1 strikingly coincides with terminal differentiation. Using brain electroporation, we show that overexpression of NeuroD1 in the periventricular region in vivo leads to the rapid appearance of cells with morphological and molecular characteristics of mature neurons in the subventricular zone and rostral migratory stream. Conversely, shRNA-induced knockdown of NeuroD1 inhibits terminal neuronal differentiation. Thus, expression of a single transcription factor is sufficient to induce neuronal differentiation of neural progenitors in regions that normally do not show addition of new neurons. These results suggest a considerable potential of NeuroD1 for use in cell-therapeutic approaches in the nervous system. adult neurogenesis | bHLH transcription factor | interneurons | postnatal electroporation
Development, 2020
Sense organs acquire their distinctive shapes concomitantly with the differentiation of sensory cells and neurons necessary for their function. Although our understanding of the mechanisms controlling morphogenesis and neurogenesis in these structures has grown, how these processes are coordinated remains largely unexplored. Neurogenesis in the zebrafish olfactory epithelium requires the bHLH proneural transcription factor Neurogenin 1 (Neurog1). To address whether Neurog1 also controls morphogenesis, we analysed the migratory behaviour of early olfactory neural progenitors in neurog1 mutant embryos. Our results indicate that the oriented movements of these progenitors are disrupted in this context. Morphogenesis is similarly affected by mutations in the chemokine receptor gene, cxcr4b, suggesting it is a potential Neurog1 target gene. We find that Neurog1 directly regulates cxcr4b through an E-box cluster located just upstream of the cxcr4b transcription start site. Our results suggest that proneural transcription factors, such as Neurog1, directly couple distinct aspects of nervous system development.
Dual Role for LIM-Homeodomain GeneLhx2in the Formation of the Lateral Olfactory Tract
The Journal of Neuroscience, 2007
The development of the olfactory system in vertebrates is a multistep process, in which several regulatory molecules are required at different stages. The development of the olfactory sensory epithelium and its projection to the olfactory bulb are both known to require the LIM-homeodomain transcription factor Lhx2. We examined whether Lhx2 plays a role in the development of the OB itself, as well as its projection to the olfactory cortex.Although there is no morphological OB protuberance in theLhx2mutant, mitral cells are normally specified and cluster in a displaced olfactory bulb-like structure (OBLS). The OBLS is not able to pioneer the lateral olfactory tract (LOT) projectionin vivoor when provided control (host) telencephalic territory in anin vitroassay. Strikingly, the mutant OBLS is capable of projecting along the LOT if provided with an existing normal LOT in the host explant. This is the first report of a role for a transcription factor expressed in the OB that selectively...