Olfactory epithelium progenitors: insights from transgenic mice and in vitro biology

Murdoch, Barbara; Roskams, A. Jane

doi:10.1007/s10735-007-9141-2

Cited by 85 publications

(117 citation statements)

References 154 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…We thus tested whether embryonic OE might contain progenitors that morphologically or antigenically resemble multipotent CNS radial glia. Nestin, an intermediate filament protein characteristic of CNS neuroepithelial stem cells (Hockfield and McKay, 1985), was detected in embryonic OE as early as E10 (Murdoch and Roskams, 2007), but was more readily detected at E13.5, in cells with a radial glia-like morphology similar to those found in embryonic olfactory bulb (OB) that were detected in every developing turbinate of the embryonic OE ( Fig. 1 A).…”

Section: Resultsmentioning

confidence: 98%

A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons

Murdoch

Roskams²

2008

J. Neurosci.

View full text Add to dashboard Cite

Persistent neurogenesis is maintained throughout development and adulthood in the mouse olfactory epithelium (OE). Despite this, the identity and origin of different embryonic OE progenitors, their spatiotemporal induction and contribution to patterning during development, has yet to be delineated. Here, we show that the embryonic OE contains a novel nestin-expressing radial glia-like progenitor (RGLP) that is not found in adult OE, which is antigenically distinct from embryonic CNS radial glia. Nestin-cre-mediated lineage tracing with three different reporters reveals that only a subpopulation of nestin-expressing RGLPs activate "CNS-specific" nestin regulatory elements, and produce spatially restricted olfactory receptor neurons (ORNs) in zone 1 of the OE, and vomeronasal receptor neurons restricted to the VR1 zone. This dorsal-medial restriction of transgene-activating cells is also seen in the embryonic OE of Nestin-GFP transgenic mice, in which green fluorescent protein (GFP) is found in a subpopulation of GFPϩMash1ϩ neuronal progenitors, despite the fact that endogenous Nestin expression is found in RGLPs throughout the OE. Embryonic OE progenitors produce three biologically distinct colony subtypes in vitro, a subpopulation of which include nestin-expressing RGLPs during in vitro colony formation. When generated from Nestin-cre/ZEG mice, neurogenic colonies also produce GFPϩMash1ϩ progenitors and ORNs. We thus identify a novel neurogenic precursor, the RGLP of the OE and vomeronasal organ (VNO), and provide the first evidence for intrinsic differences in the origin and spatiotemporal potential of distinct progenitors during development of the OE and VNO.

show abstract

Section: Resultsmentioning

confidence: 98%

A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons

Murdoch

Roskams²

2008

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…6J; Table 2). SPARC is present in OEC processes (nestin/BLBP-positive) (Murdoch and Roskams, 2007) that surround the outside of olfac- tory axon bundles (Fig. 6I inset is in cross-section).…”

Section: Sparc Is Expressed By Schwann Cells and Olfactory Ensheathinmentioning

confidence: 99%

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed during development, tissue remodeling, and repair. SPARC produced by olfactory ensheathing cells (OECs) can promote axon sprouting in vitro and in vivo. Here, we show that in the developing nervous system of the mouse, SPARC is expressed by radial glia, blood vessels, and other pial-derived structures during embryogenesis and postnatal development. The rostral migratory stream contains SPARC that becomes progressively restricted to the SVZ in adulthood. In the adult CNS, SPARC is enriched in specialized radial glial derivatives (Mü ller and Bergmann glia), microglia, and brainstem astrocytes. The peripheral glia, Schwann cells, and OECs express SPARC throughout development and in maturity, although it appears to be down-regulated with maturation. These data suggest that SPARC may be expressed by glia in a spatiotemporal manner consistent with a role in cell migration, neurogenesis, synaptic plasticity, and angiogenesis.

show abstract

“…In the OE, two subpopulations of basal cells have been proposed to function as tissue stem cells; globose basal cells (GBCs) are the major proliferating cell population within the adult OE, and horizontal basal cells (HBCs) are relatively quiescent cells that lie just above the basal lamina. HBCs express the epithelial markers keratin 5 (K5) and CD54 (also known as ICAM-1), and HBCs express the stem cell markers Pax6 and Sox2 [5][6][7][8]. Although the evidence collected to date is far from conclusive, it has been suggested that HBCs are the tissue stem cells in the OE because HBCs can self-renew and generate neuronal and non-neuronal cells, including the GBCs, in vivo (both during normal turnover and following OE injury) as well as in vitro [4,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Horizontal Basal Cell-Specific Deletion ofPax6Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury

Suzuki

Sakurai

Yamazaki

et al. 2015

Stem Cells and Development

View full text Add to dashboard Cite

In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal's lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6 and are considered relatively quiescent tissue stem cells in the OE. Pax6 is a key regulator of several developmental processes in the central nervous system and in sensory organs. Although Pax6 is expressed in the OE, its precise role remains unknown, particularly with respect to stem celllike HBCs. To investigate the function of Pax6 in the developmental and regenerative processes in the OE, we generated conditional Pax6-knockout mice carrying a loxP-floxed Pax6 gene. Homozygous Pax6-floxed mice were crossed with K5-Cre transgenic mice to generate HBC-specific Pax6-knockout (Pax6-cKO) mice. We confirmed that the deletion of Pax6 expression in HBCs was sufficiently achieved in zone 1 of the OE in Pax6-cKO mice 3 days after methimazole-induced severe damage. In this condition, regeneration of the OE was dramatically impaired; both OE thickness and the number of ORNs were significantly decreased in the regenerated OE of Pax6-cKO mice. These results suggest that Pax6 expression is essential for HBCs to differentiate into neuronal cells during the regeneration process following severe injury.

show abstract

Olfactory epithelium progenitors: insights from transgenic mice and in vitro biology

Cited by 85 publications

References 154 publications

A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons

A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Horizontal Basal Cell-Specific Deletion ofPax6Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury

Contact Info

Product

Resources

About