Notch signalling pathway mediates hair cell development in mammalian cochlea

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.     

Engineering a mouse balancer chromosome.

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.     

Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat

In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.     

Immunoactive TSH in the amniotic fluid of the rat

Summary Amniotic fluid was obtained from 19-day-old rat fetuses by aspiration. Pooled samples measured at 4 different dilutions demonstrated parallelism with standard rat TSH. It is concluded that rat amniotic fluid has TSH immunoactivity.This work was supported by Hong Kong University Research Grant No. 335/034/5727.The authors wish to acknowledge with thanks the gift of rat TSH RIA kit from Dr A. F. Parlow and the Rat Pituitary Programme of NIAMDD.     

A rat mutant unable to synthesize vitamin C

Summary A colony of Wistar rats with a hereditary defect in L-ascorbic acid-synthesizing ability was established. This rat, like primates and guinea pigs, lacks L-gulonolactone oxidase (EC 1.1.3.8) which catalyzes the last step of L-ascorbic acid biosynthesis. When L-ascorbic acid was added to their drinking water, the rats grew almost normally and were fertile. These mutant rats should be useful not only for nutritional and parmacological studies on vitamin C but also for genetic studies on the lack of this enzyme.Acknowledgments. We are indebted to K. Katagiri, the previous director of Aburahi Laboratories, for his encouragement during the experiment. We are also grateful to H. Nishimura, Professor Emeritus of Kyoto University, and Y. Hasegawa of our laboratory for their helpful suggestions.     

Determination of polyamine oxidase activities in human tissues

A very simple fluorometric assay for polyamine oxidase (PAO) in tissues, with N1-monoacetylspermine as substrate, is described. The PAO was present in all human organs tested; it was highest in the liver, followed by the testis, kidney, spleen and small intestine.