Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important coordinated somite segmentation. However, the molecular mechanism such remains to be determined. Here, we show that serum treatment cultured cells induces cyclic expression both mRNA protein effector Hes1, a basic helix-loop-helix (bHLH) factor, periodicity. Cycling cell-autonomous depends on negative autoregulation hes1 transcription...

Radial glial cells derive from neuroepithelial cells, and both cell types are identified as neural stem cells. Neural known to change their competency over time during development: they initially undergo self-renewal only then give rise neurons first later. Maintenance of until late stages is thus believed be essential for generation in correct numbers diverse types, but little about how the timing differentiation regulated its deregulation influences brain organogenesis. Here, we report...

Abstract Five N‐methyl‐D‐aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we analyzed the expression patterns of mRNAs for NMDA in developing adult rats by situ hybridization. The developmental changes were most salient cerebellum. In external granular layer, hybridization signals mRNAs, NR2C appeared postnatal day 3, but no NR2D mRNA was expressed at any stage examined. NR1 all cerebellar neurons stages NR2A Purkinje cells granule...

The basic helix–loop–helix (bHLH) gene Hes7 , a putative Notch effector, encodes transcriptional repressor. Here, we found that expression oscillates in 2-h cycles the presomitic mesoderm (PSM). In -null mice, somites are not properly segmented and their anterior–posterior polarity is disrupted. As result, somite derivatives such as vertebrae ribs severely disorganized. Although of its ligands affected significantly, oscillator modulator lunatic fringe expressed continuously throughout...

Hes7 , a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that protein is also expressed dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed and Lunatic fringe ( Lfng ) transcription occurs protein-negative domains. Furthermore, constitutively up-regulated absence down-regulated by stabilization protein. Thus, periodic repression critical this negative feedback represents...

ABSTRACT We have isolated the basic helix-loop-helix (bHLH) gene Hes6, a novel member of family mammalian homologues Drosophila hairy and Enhancer split. Hes6 is expressed by both undifferentiated differentiated cells, unlike Hes1, which only former cells. alone does not bind to DNA but suppresses Hes1 from repressing transcription. In addition, inhibiting Mash1-E47 heterodimer thereby enables Mash1 E47 upregulate transcription in presence Hes1. Furthermore, misexpression with retrovirus...

Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and mouse expressed prominently in endothelial cell lineage embryos. We generated mice deficient found that embryos died utero at embryonic day 10.5-11.5, manifesting marked abnormalities vascular development. Vascular remodeling was impaired brain yolk sac, major trunk veins were not formed. In vitro para-aortic splanchnopleural explant...

The basic helix-loop-helix genes Math3 and NeuroD are expressed by differentiating amacrine cells, retinal interneurons. Previous studies have demonstrated that a normal number of cells is generated in mice lacking either or NeuroD. We found that, Math3-NeuroD double-mutant retina, completely missing, while ganglion Müller glial increased number. In the would normally differentiate into did not die but adopted cell fates. Misexpression using developing explant cultures showed although alone...

The neuropeptide-inducing activity of neurotrophic factors was tested in cultured cerebral cortical neurons. Brain-derived factor (BDNF) specifically increased contents the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY), but its effect on cholecystokinin octapeptide GABA much less significant. maximal induction NPY content (15-fold increase) achieved by 20 ng/ml BDNF. These changes were also reproduced at mRNA level. In contrast, neurotrophin-3 potent increasing SOM contents,...

Background: Whereas Notch signalling is essential for somitogenesis, mice deficient the basic helix‐loop‐helix (bHLH) genes Hes1 and Hes5 , downstream effectors, display normal somite formation, indicating that there may be an as‐yet unidentified ‐related bHLH gene. Results: We identified a novel gene, designated Hes7 from mouse embryos. has conserved domain in amino‐terminal region WRPW at carboxy‐terminal end, like Hes1. The gene located next to Aloxe3 which mapped position 37.0 cM...

Neural precursor cells proliferate in the ventricular zone while giving rise to neurons of deep layers first, then those superficial layers, and lastly, glial brain. Thus, it is essential maintain neural until late stages development for generation a wide variety cell types. Here, we found that Hes-related basic helix-loop-helix (bHLH) genes Hesr1/Hey1 Hesr2/Hey2 are expressed zone, which contains cells. Misexpression Hesr1 Hesr2 by electroporation mouse brain at embryonic day 13.5...

Retinal precursor cells give rise to six types of neurons and one type glial cell during development, this process is controlled by multiple basic helix-loop-helix (bHLH) genes. However, the precise mechanism for specification retinal neuronal subtypes, particularly horizontal photoreceptors, remains be determined. Here, we examined retinas with three different combinations triple bHLH gene mutations. In lacking genes Ngn2, Math3, NeuroD, as well other such bipolar were severely decreased in...

Segmentation of the vertebrate body axis is initiated through somitogenesis, whereby epithelial somites bud off in pairs periodically from rostral end unsegmented presomitic mesoderm (PSM). The periodicity somitogenesis governed by a molecular oscillator that drives periodic waves clock gene expression caudo-rostrally PSM with matches somite formation. To date genes comprise components Notch, Wnt, and FGF pathways. literature contains controversial reports as to absolute role(s) Notch...

Abstract Retinal stem cells (RSCs) are present in the ciliary margin of adult human eye and can give rise to all retinal cell types. Here we show that modulation transcription factor gene expression RSCs greatly enriches photoreceptor progeny, strong enrichment was obtained with combined transduction OTX2 CRX together CHX10. When these genetically modified RSC progeny transplanted into mouse eyes, their integration differentiation is superior unmodified progeny. Moreover, electrophysiologic...

Vertebrate segments called somites are generated by periodic segmentation of the anterior extremity presomitic mesoderm (PSM). During somite in zebrafish, mesp-b determines a future boundary at position B-2 within PSM. Heat-shock experiments, however, suggest that an earlier exists B-5, but molecular signature this remains unidentified. Here, we characterized fibroblast growth factor (FGF) signal activity PSM, and demonstrated limit downstream Erk corresponds to B-5 boundary. Moreover, clock...

Members of a subclass hairy/Enhancer split [E(spl)] homologs, called hesr genes, are structurally related to another hairy/E(spl) Hes which play an important role in neural development. To characterize the roles genes development, we used retina as model system. In situ hybridization analysis indicated that all expressed developing retina, but only hesr2 expression is associated spatially with gliogenesis. Each member was then misexpressed retrovirus retinal explant cultures prepared from...

The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), key required the left–right asymmetric body plan in zebrafish, generated from cluster ∼20 dorsal forerunner (DFCs). Although several genes are known to be involved KV formation, how DFC clustering regulated and then contributes remain unclear. Here we show that positive feedback regulation FGF signaling by Canopy1 (Cnpy1) controls clustering. Cnpy1 positively...

Little is known about how the sizes of animal tissues are controlled. A prominent example somite size which varies widely both within an individual and across species. Despite intense study segmentation clock governing timing generation, it relates to poorly understood. Here we examine scaling find that at specification scales with length presomitic mesoderm (PSM) despite considerable variation in PSM developmental stages surgically size-reduced embryos. Measurement period, axis elongation...

Neuronal subtype specification depends on multiple transcription factors such as basic helix-loop-helix (bHLH) factors. However, factor codes for most neurons remain to be determined. Here, we report identification of a novel mouse bHLH factor, termed Heslike, that has Hes1-like domain and transcriptional repressor activity. Heslike is coexpressed with the Mash1 in brain regions give rise GABAergic neurons. In mesencephalon caudal diencephalon, coexpression initially restricted small but...

The number of vertebrae is defined strictly for a given species and depends on the somites, which are earliest metameric structures that form in development. Somites formed by sequential segmentation. periodicity somite segmentation orchestrated synchronous oscillation gene expression presomitic mesoderm (PSM), termed "somite clock," Notch signaling plays crucial role. Here we show clock period sensitive to activity, fine-tuned its feedback regulator, Notch-regulated ankyrin repeat protein...