Haemoglobins and myoglobins constitute related protein families that function in oxygen transport and storage in humans and other vertebrates. Here we report the identification of a third globin type in man and mouse. This protein is predominantly expressed in the brain, and therefore we have called it neuroglobin. Mouse neuroglobin is a monomer with a high oxygen affinity (half saturation pressure, P50 approximately 2 torr). Analogous to myoglobin, neuroglobin may increase the availability of oxygen to brain tissue. The human neuroglobin gene (NGB), located on chromosome 14q24, has a unique exon-intron structure. Neuroglobin represents a distinct protein family that diverged early in metazoan evolution, probably before the Protostomia/Deuterostomia split.

The diversity of neuronal nicotinic receptors (nAChRs) in addition to their possible involvement in such pathological conditions as Alzheimer's disease have directed our research towards the characterization of these receptors in various mammalian brain areas. Our studies have relied on electrophysiological, biochemical, and immunofluorescent techniques applied to cultured and acutely dissociated hippocampal neurons, and have been aimed at identifying the various subtypes of nAChRs expressed in the mammalian central nervous system (CNS), at defining the mechanisms by which CNS nAChR activity is modulated, and at determining the ion permeability of CNS nAChR channels. Our findings can be summarized as follows: (1) hippocampal neurons express at least three subtypes of CNS nAChRs--an alpha 7-subunit-bearing nAChR that subserves fast-inactivating, alpha-BGT-sensitive currents, which are referred to as type IA, and alpha 4 beta 2 nAChR that subserves slowly inactivating, dihydro-beta-erythroidine-sensitive currents, which are referred to as type II, and an alpha 3 beta 4 nAChR that subserves slowly inactivating, mecamylamine-sensitive currents, which are referred to as type III; (2) nicotinic agonists can activate a single type of nicotinic current in olfactory bulb neurons, that is, type IA currents; (3) alpha 7-subunit-bearing nAChR channels in the hippocampus have a brief lifetime, a high conductance, and a high Ca2+ permeability; (4) the peak amplitude of type IA currents tends to rundown with time, and this rundown can be prevented by the presence of ATP-regenerating compounds (particularly phosphocreatine) in the internal solution; (5) rectification of type IA currents is dependent on the presence of Mg2+ in the internal solution; and (6) there is an ACh-insensitive site on neuronal and nonneuronal nAChRs through which the receptor channel can be activated. These findings lay the groundwork for a better understanding of the physiological role of these receptors in synaptic transmission in the CNS.

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We asked whether specifications of different regions of the rodent and avian telencephalon during development involved the acquisition of differential adhesive properties. Cells from different regions were aggregated in a short-term aggregation assay, and their segregation was analyzed. Both neurons and precursor cells from cortex segregate from striatal cells at early, but not later, stages, whereas cells from rodent neocortex and hippocampus segregated only during later stages. Segregation was abolished when Ca2+-dependent but not Ca2+-independent adhesion molecules were selectively removed. Thus, selective adhesion appears to be a conserved mechanism that restricts cellular mixing and might serve to maintain positional information during forebrain development. A candidate for mediating the Ca2+-dependent segregation is the CD15 (Lewis(x)) carbohydrate epitope, which is selectively expressed by mammalian cortex but not striatum.

Molecules regulating morphogenesis by cell‐cell interactions are the cadherins, a class of calcium‐dependent adhesion molecules. One of its members, M‐cadherin, has been isolated from a myoblast cell line (Donalies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024—8028). In mouse development, expression of M‐cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be down‐regulated in developing muscle masses (Moore and Walsh [1993] Development 117:1409—1420). Affinity‐purified polyclonal M‐cadherin antibodies, detecting a protein of approximately 120 kDa, were used to study the cell expression pattern of M‐cadherin protein. It was first visualized in somites at E10 1/3 and could be confined to desmin positive, myotomal cells. At all subsequent prenatal stages, M‐cadherin was only found in myogenic cells of somitic origin. The detection of the protein at E10 1/3 suggests a translational delay of M‐cadherin mRNA of 1 to 2 days (E8.5 vs. E10 1/3). This was further supported by the finding that during differentiation of ES cell line BLC6 into skeletal muscle cells in culture, expression of M‐cadherin mRNA can be detected 2 days prior to M‐cadherin protein. During prenatal development, the pattern of M‐cadherin expression changes: In E10 1/3 embryos and also in myotomal cells of later stages, M‐cadherin is evenly distributed on the cell surface. In developing muscle masses (tested at E16 to E18), however, M‐cadherin protein becomes clustered most likely at sites of cell‐cell contact as indicated by double‐labelling experiments: M‐cadherin‐staining is the positive image of laminin negative areas excluding the presence of a basal lamina at M‐cadherin positive sites. Furthermore, M‐cadherin is coexpressed with the neuronal cell adhesion molecule N‐CAM which has been shown to mediate cell‐cell contact in myogenic cells. In summary, our results are in line with the idea that M‐cadherin might play a central role in myogenic morphogenesis. © 1994 Wiley‐Liss, Inc.