Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development.

The sensory patches in the vertebrate inner ear are similar in function to the mechanosensory bristles of a fly, and consist of a similar set of cell types. If they are truly homologous structures, they should also develop by similar mechanisms. We examine the genesis of the neurons, hair cells and supporting cells that form the sensory patches in the inner ear of the chick. These all arise from the otic epithelium, and are produced normally even in otic epithelium cultured in isolation, confirming that their production is governed by mechanisms intrinsic to the epithelium. First, the neuronal sublineage becomes separate from the epithelial: between E2 and E3.5, neuroblasts delaminate from the otocyst. The neuroblasts then give rise to a mixture of neurons and neuroblasts, while the sensory epithelial cells diversify to form a mixture of hair cells and supporting cells. The epithelial patches where this occurs are marked from an early stage by uniform and maintained expression of the Notch ligand Serrate1. The Notch ligand Delta1 is also expressed, but transiently and in scattered cells: it is seen both early, during neuroblast segregation, where it appears to be in the nascent neuroblasts, and again later, in the ganglion and in differentiating sensory patches, where it appears to be in the nascent hair cells, disappearing as they mature. Delta-Notch-mediated lateral inhibition may thus act at each developmental branchpoint to drive neighbouring cells along different developmental pathways. Our findings indicate that the sensory patches of the vertebrate inner ear and the sensory bristles of a fly are generated by minor variations of the same basic developmental program, in which cell diversification driven by Delta-Notch and/or Serrate-Notch signalling plays a central part.

A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis.

In the Drosophila nervous system, lateral inhibition regulates commitment to a neural fate by preventing neighbouring cells from developing alike. This signalling process is mediated by two transmembrane proteins-Notch as receptor and Delta as its ligand. The Delta-related protein Serrate also acts as a Notch ligand in Drosophila, but in a different developmental process that organizes patterning of the wing. We have previously shown that lateral inhibition operates at early stages of neurogenesis in vertebrates, via genes homologous to Drosophila Delta and Notch. We report here the cloning of a chick Serrate homologue, C-Serrate-1. This gene is expressed in the central nervous system, as well as in the cranial placodes, nephric epithelium, vascular system, and distal limb-bud mesenchyme. In most of these sites, its expression is associated with expression of C-Notch-1 and C- Delta-1. All three genes are expressed in the ventricular zone of the hindbrain and spinal cord, throughout the period when neurons are being born. Within this zone, C-Delta-1 and C-Serrate-1 are expressed in complementary subsets of nondividing cells that appear to be nascent neurons: C- Serrate-1 expression is restricted to specific locations along the dorsoventral axis, forming narrow bands extending from the anterior hindbrain to the tail. Our observations strongly suggest that Delta-Notch signalling delivers lateral inhibition not only early but throughout vertebrate neurogenesis to regulate neuronal commitment, and that Serrate-Notch signalling may act similarly in this process. By analogy with its role in Drosophila wing patterning, C-Serrate-1 may also have a role in organising the dorso-ventral pattern of the neural tube. We argue that signalling via Notch maintains neurogenesis, both in vertebrates and in flies, by keeping a proportion of the neuroepithelial cells in an uncommitted stem-cell-like state.

Expression of a Delta homologue in prospective neurons in the chick.

The product of the Delta gene, acting as ligand, and that of the Notch gene, acting as receptor, are key components in a lateral-inhibition signalling pathway that regulates the detailed patterning of many different tissues in Drosophila. During neurogenesis in particular, neural precursors, by expressing Delta, inhibit neighbouring Notch-expressing cells from becoming committed to a neural fate. Vertebrates are known to have several Notch genes, but their functions are unclear and their ligands hitherto unidentified. Here we identify and describe a chick Delta homologue, C-Delta-1. We show that C-Delta-1 is expressed in prospective neurons during neurogenesis, as new cells are being born and their fates decided. Our data from the chick, combined with parallel evidence from Xenopus, suggest that both the Delta/Notch signalling mechanism and its role in neurogenesis have been conserved in vertebrates.

A Japanese encephalitis focus in Bangladesh.

This paper describes a focus of Japanese encephalitis in Modhupur Forest area, Bangladesh. The disease was diagnosed for the first time in Bangladesh. The diagnosis was based on the clinical picture of the disease and the results of serological investigations; the causative agent could not be isolated. During 2 year's surveillance of the focus, no new cases of the disease were recorded. Only 1.9% of 1046 healthy persons tested showed HI antibodies against group B arboviruses, and no virus was isolated from 41 mosquito pools. These results indicate that the disease was introduced into the area, produced an outbreak and later died out.