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Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism. The existence of a 'stem cell niche' was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells. Since then, an increasing body of work has focused on defining stem cell niches. Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells . Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the most striking aspects of all auditory and vestibular sensory epithelia is the mosaic pattern of hair cells and supporting cells. The factors that are required for the development of this mosaic have not been determined, however the results of recent studies have demonstrated that components of the neurogenic (Notch) signaling pathway are expressed in the developing inner ears of a number of different vertebrate species. To examine whether this signaling pathway may play a similar role in the development of the hair cell mosaic in the mammalian vestibular system, the expression patterns of proneural (Math1) and neurogenic (Notch1, Jagged2, HES5) genes were examined in the developing mouse inner ear. Results indicate that Notch1 is initially expressed throughout the developing inner ear and becomes restricted to non-sensory cells within the developing sensory epithelia. In contrast, initial expression of Math1 and Jagged2 is localized to the developing sensory epithelia and ultimately becomes restricted to hair cells. Interestingly, transcripts for HES5, a target of Notch activation, are expressed in the developing cristae but not in the saccule or utricle. These results are consistent with the hypothesis that formation of the hair cell mosaic is regulated through the neurogenic pathway. However the differential expression of HES5 within the ear indicates that the downstream targets of Notch1 activation are not consistent across all of the sensory epithelia and suggests that the effects of activation of Notch1 in the saccule and utricle must be regulated through alternate target genes. [ABSTRACT FROM AUTHOR]

The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic. [ABSTRACT FROM AUTHOR]

Presents research which showed that mice homozygous for a targeted mutation of the lunatic fringe (Lfng) gene have defects in somite formation and anterior-posterior patterning of the somites. Development of segmentation in vertebrates; Role of the Notch signaling pathway; Fringe gene in Drosophila; Irregularities of somites; Results of marker analysis; Importance of Lfng encoding.

The article discusses a study conducted by P. Bi and colleagues on the multiple roles played by Notch signalling in the regulation of adipose browning and energy homeostasis in mammals. It mentions the deletion of gene encoding the Notch 1 receptor or the gene encoding the Notch signaling pathway primary transcriptional effector by the authors to assess the direct relationship between Notch signaling levels and brown adipose tissue (BAT).

The article presents a discovery of the new role of Notch pathway in vascular biology. An over view of the papers published in the journal on vascular endothelial growth factor (VEGF) and Notch signaling pathways and role for Dll 4 Notch signaling during vascular development, is presented. The new findings are supposed to help a better understanding of cancer and in the treatment of it.

The authors focus on the laser surgery on mice which are subjected to genetic testing. In order to accelerate phenotype analysis, mutant mice from embryonic stem cells are being generated. The eight cell microinjection procedure in two approaches is being suggested for production of homozygotes. The authors conclude that the need for cost effectiveness for breeding, phenotyping and maintaining the mice will be met by laser surgery.

Offers background and analysis of a paper that provides important data linking the Notch signalling pathway to familial causes of stroke in humans. The familial syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); The study by Tournier-Lasserve and colleagues found in the October 24, 1996 issue of `Nature'; The possible relationship to Alzheimer's disease.