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N Osumi

Publications and source records attributed to N Osumi.

25 records · Page 2Linked to original sources
PubMed1999

Expression of receptor tyrosine kinase RYK in developing rat central nervous system.

Receptor tyrosine kinase RYK is a mammalian homologue of Drosophila Lio, which is involved in learning and memory and in axon guidance. We cloned a rat ryk gene and characterized its expression pattern in the central nervous system. Northern blot analysis of the whole brain revealed that the RYK mRNA was abundant during the period from 13 to 18 embryonic days (E13-18) and it decreased by E20. In the postnatal brain, the RYK signal was higher in postnatal one week (P1W) cerebrum and in P2W cerebellum than in later stages. In situ hybridization revealed that RYK was expressed throughout the central nervous system, mainly in the ventricular zone on E11 and E13. On E18 and E20, the remarkable level of RYK mRNA was detected in the ventricular zone as well as in the cortical plate of the forebrain. These two regions overlapped the immunoreactive areas of nestin and MAP2, a neural stem cell marker and a mature neural marker, respectively. Moreover, the double-labeling analysis showed that the same cells expressed both RYK and nestin in the ventricular zone. In the postnatal brain, RYK was predominantly expressed in neurons of various regions. These observations suggest that RYK plays a contributory role as a multifunctional molecule in the differentiation and maturation of neuronal cells in the central nervous system.

Animals↗
PubMed1999

Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system.

Like other tissues and organs in vertebrates, multipotential stem cells serve as the origin of diverse cell types during genesis of the mammalian central nervous system (CNS). During early development, stem cells self-renew and increase their total cell numbers without overt differentiation. At later stages, the cells withdraw from this self-renewal mode, and are fated to differentiate into neurons and glia in a spatially and temporally regulated manner. However, the molecular mechanisms underlying this important step in cell differentiation remain poorly understood. In this study, we present evidence that the expression and function of the neural-specific transcription factors Mash-1 and Prox-1 are involved in this process. In vivo, Mash-1- and Prox-1-expressing cells were defined as a transient proliferating population that was molecularly distinct from self-renewing stem cells. By taking advantage of in vitro culture systems, we showed that induction of Mash-1 and Prox-1 coincided with an initial step of differentiation of stem cells. Furthermore, forced expression of Mash-1 led to the down-regulation of nestin, a marker for undifferentiated neuroepithelial cells, and up-regulation of Prox-1, suggesting that Mash-1 positively regulates cell differentiation. In support of these observations in vitro, we found specific defects in cellular differentiation and loss of expression of Prox-1 in the developing brain of Mash-1 mutant mice in vivo. Thus, we propose that induction of Mash-1 and Prox-1 is one of the critical molecular events that control early development of the CNS.

Animals↗
PubMed1998

Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo.

The cloning of the full-length cDNA encoding meltrin beta (ADAM19), one of the metalloprotease-disintegrins expressed in mouse myogenic cells, revealed that the meltrin beta gene encodes a membrane protein closely related to meltrin alpha (ADAM12) which participates in myotube formation in vitro. To delineate the functions of meltrin alpha and beta, we examined the expression patterns of their transcripts during embryogenesis. The meltrin alpha gene is activated in condensed mesenchymal cells that give rise to skeletal muscle, bones and visceral organs. Meltrin beta mRNA, in contrast, is markedly expressed in craniofacial and dorsal root ganglia and ventral horns of the spinal cord, where peripheral neuronal cell lineages differentiate. Heart, skeletal muscle, intestine and lung also express meltrin beta mRNA transiently. Although the meltrin alpha and beta transcripts exhibit distinct expression patterns during embryogenesis, both genes are mainly activated in mesenchymal cells that are derived from both mesoderm and ectoderm.

ADAM Proteins↗
PubMed1998

Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos.

Classical transplantation experiments with various amphibian tissues have shown that tooth development requires not only oral ectoderm and neural crest but also foregut endoderm. In addition, histological observation of oral membrane showed that the tooth germs are initiated in some ectodermal cells and neural crest cells adjacent to foregut endoderm. These studies suggest that tooth initiation requires the presence and cooperation of these three components. In mammals, however, there is no direct evidence that tooth formation is involved in the region of oral ectoderm adjacent to foregut endoderm. In order to elucidate the contribution of foregut endoderm to tooth formation, we established a new type of endodermal cell tracing system with a recombinant adenovirus called Adex-lacZ, and performed endodermal cell tracing in a long-term culture system. Cells labelled with Adex-lacZ were seen next to non-labelled thickening epithelium, presumptive incisor epithelium. These findings show the first direct evidence in mammals that tooth formation takes place in the specified part of oral ectoderm adjacent to foregut endoderm, suggesting that foregut endoderm plays a role in tooth initiation.

Adenoviridae↗
PubMed1997

Pax-6 is involved in the specification of hindbrain motor neuron subtype.

Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2 exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos. By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

Animals↗