Schwarting Gerald A, Gridley Thomas, Henion Timothy R
Shriver Center/UMMS, 200 Trapelo Road, Waltham, MA 02452, USA.
J Mol Histol. 2007 Dec;38(6):543-53. doi: 10.1007/s10735-007-9110-9. Epub 2007 Jun 29.
Despite the relatively simplified organization of the olfactory epithelium (OE), our understanding of the factors that regulate its cellular diversity is limited. Genetic and localization studies suggest that Notch signaling may be important in this process. We characterize here a population of Notch1 (+) olfactory basal cells in embryonic mice that coordinately express both the Notch effector Hes5 and the glycosyltransferase Lfng. These cells are distinct from Mash1(+) neuronal precursors, but give rise to sensory neurons, suggesting that Notch1 signals may in part function to maintain a neurogenic progenitor pool. Furthermore, Lfng(+) cells also generate a population of cells in the migratory mass that appear to be ensheathing glial precursors, indicating potential multipotency in these progenitors. The Notch ligand Dll4 is expressed by basal OE cells that are interspersed with Notch1(+) progenitors during later OE neurogenesis. In contrast, mice deficient in Dll1 exhibit a smaller OE and a loss of Hes5 expression, indicating an earlier function in olfactory progenitor cell development. Taken together, these results further support a role for Notch signaling in the regulation of olfactory neurogenesis and cell diversity.
尽管嗅觉上皮(OE)的组织结构相对简单,但我们对调节其细胞多样性的因素的了解仍然有限。基因和定位研究表明,Notch信号通路可能在此过程中发挥重要作用。我们在此描述了胚胎小鼠中一群Notch1(+)嗅觉基底细胞,它们同时协调表达Notch效应分子Hes5和糖基转移酶Lfng。这些细胞不同于Mash1(+)神经元前体,但可产生感觉神经元,这表明Notch1信号可能部分起到维持神经源性祖细胞池的作用。此外,Lfng(+)细胞还在迁移团中产生一群细胞,这些细胞似乎是成鞘胶质前体,表明这些祖细胞具有潜在的多能性。在后期的OE神经发生过程中,Notch配体Dll4由与Notch1(+)祖细胞相间分布的基底OE细胞表达。相反,Dll1缺陷的小鼠表现出较小的OE且Hes5表达缺失,表明其在嗅觉祖细胞发育中具有早期功能。综上所述,这些结果进一步支持了Notch信号通路在调节嗅觉神经发生和细胞多样性中的作用。