Article

Horizontal basal cells are multipotent progenitors in normal and injured adult olfactory epithelium.

Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Stem Cells (impact factor: 7.78). 06/2008; 26(5):1298-306. DOI:10.1634/stemcells.2007-0891
Source: PubMed

ABSTRACT The mammalian olfactory neuroepithelium provides a unique system for understanding the regulation of neurogenesis by adult neural stem cells. Recently, mouse horizontal basal cells (HBCs) were identified as stem cells that regenerate olfactory receptor neurons (ORNs) and non-neuronal cell types only after extensive injury of the olfactory epithelium (OE). Here we report a broader spectrum of action for these cells. We show that even during normal neuronal turnover, HBCs actively generate neuronal and non-neuronal cells throughout adulthood. This occurs in a temporally controlled manner: an initial wave of HBC-derived neurogenesis was observed soon after birth, and a second wave of neurogenesis was observed at 4 months of age. Moreover, upon selective depletion of mature ORNs by olfactory bulbectomy, HBCs give rise to more neurons. Our findings demonstrate a crucial role for HBCs as multipotent progenitors in the adult OE, acting during normal neuronal turnover as well as in acute regeneration upon injury.

0 0
 · 
0 Bookmarks
 · 
21 Views
  • Source
    Article: Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome.
    W S Layman, D P McEwen, L A Beyer, S R Lalani, S D Fernbach, E Oh, A Swaroop, C C Hegg, Y Raphael, J R Martens, D M Martin
    [show abstract] [hide abstract]
    ABSTRACT: Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.
    Human Molecular Genetics 04/2009; 18(11):1909-23. · 7.64 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

4 months
 
acute regeneration
 
adult neural
 
adult OE
 
adulthood
 
broader spectrum
 
crucial role
 
extensive injury
 
HBC-derived neurogenesis
 
initial wave
 
mammalian olfactory neuroepithelium
 
mouse horizontal basal cells
 
multipotent progenitors
 
non-neuronal cell types
 
non-neuronal cells
 
normal neuronal turnover
 
regenerate olfactory receptor neurons
 
second wave
 
selective depletion
 
unique system
 

Naomi Iwai