The Drosophila neuralized gene encodes a C3HC4 zinc finger.

Price, Brendan D.; Chang, Zhen; Smith, Roger K.; Bockheim, S.; Laughon, Allen

doi:10.1002/j.1460-2075.1993.tb05895.x

Cited by 45 publications

(35 citation statements)

References 66 publications

(31 reference statements)

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“…Neur consists of two copies of a novel domain referred to as ''neuralized homology repeat'' and a C-terminal RING finger (27,28). When activated by using GMR-Gal4, wild-type Neur, Neur deleted for the RING finger (Neur⌬RF), and the Neur RING finger alone (Neur RING) could all cause an adult rough eye phenotype.…”

Section: Fig 3 Requirements Of N-pathway Members For Cone Cell Indumentioning

confidence: 99%

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neuralized is essential for a subset of Notch pathway-dependent cell fate decisions during Drosophila eye development

Lai

Rubin

2001

Proc. Natl. Acad. Sci. U.S.A.

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neuralized (neur) is a neurogenic mutant of Drosophila in which many signaling events mediated by the Notch (N) receptor are disrupted. Here, we analyze the role of neur during eye development. Neur is required in a cell-autonomous fashion to restrict R8 and other photoreceptor fates and is involved in lateral inhibition of interommatidial bristles but is not required for induction of the cone cell fate. The latter contrasts with the absolute requirement for Suppressor of Hairless and the Enhancer of split-Complex for cone cell induction. Using gain-of-function experiments, we further demonstrate that ectopic wild-type and truncated Neur proteins can interfere with multiple N-controlled aspects of eye development, including both neur-dependent and neur-independent processes. The Drosophila eye has been a particularly useful model system for studies of cell-cell interactions during formation of a biological pattern. The adult eye consists of some 800 identical ommatidia; each is a complete unit eye containing 20 cells, including 8 photoreceptors and 12 accessory cells. The proper commitment of cell fates in the eye depends on both inhibitory and inductive cell-cell interactions mediated by multiple signaling cascades (1).The Notch (N) receptor is directly involved in the determination of all cell types in the Drosophila eye, in addition to having other functions in controlling growth and polarity of the eye (2-6). N has two opposing functions with regard to early eye neurogenesis. It first promotes R8 photoreceptor differentiation by enhancing expression of the proneural gene for photoreceptors, atonal (7,8). R8 is the first cell fate to differentiate in the eye and is required for recruitment of all other photoreceptors; N clones lack photoreceptors (8,9). N is subsequently involved in restriction of the R8 fate, because a temporally restricted reduction in N function results in the differentiation of clusters of ectopic R8 cells (10). Other experiments performed during larval and pupal development further demonstrated that N is involved in the determination of outer photoreceptors, cone cells, pigment cells, and bristles (2). N thus appears to be required for all stages of ommatidial assembly.A central ''core'' of proteins involved in the N pathway appears to be deployed in a wide variety of settings of N-pathway activity in invertebrates as well as vertebrates (11). The basic scaffold of the N pathway, as it is most often used, appears to be as follows. Interaction of the transmembrane ligand Delta with the transmembrane receptor Notch results in the release of a proteolytic fragment including the intracellular domain of Notch (N IC ) (12)(13)(14). N IC then translocates to the nucleus, where it acts as a coactivator for the sequence-specific DNA-binding protein Suppressor of Hairless [Su(H)] (15, 16). This complex activates transcription of various target genes, which include multiple members of the Enhancer of split-Complex [E(spl)-C] (17-21).Mutations in neuralized (neur) result in a variety of developmenta...

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Section: Fig 3 Requirements Of N-pathway Members For Cone Cell Indumentioning

confidence: 99%

“…neur encodes a protein of unknown function, consisting of two copies of a novel protein domain (the ''neuralized homology repeat'') and a C-terminal RING domain (26)(27)(28). In this report, we investigate the role of neur and find that it regulates a subset of N-controlled processes during eye development.…”

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confidence: 97%

neuralized is essential for a subset of Notch pathway-dependent cell fate decisions during Drosophila eye development

Lai

Rubin

2001

Proc. Natl. Acad. Sci. U.S.A.

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“…In the nervous system, the Notch signaling mechanism is involved in neurogenesis (1, 3), neuronal differentiation (2, 6), axon path finding (7,8), and neurite growth (9, 10). The importance of Notch in maintaining normal neuronal function in the adult has been revealed by a number of human neurological syndromes because of defects in Notch signaling (6).Like Notch, the Drosophila neuralized gene (neu) is a neurogenic gene whose function is to limit the number of neuronal precursor cells and to specify sensory organ as well as R8 photoreceptor cell fates (11)(12)(13)(14)(15)(16)(17). Genetic analyses suggest that neuralized interacts with other neurogenic genes, such as the Notch receptor and the Delta ligand for cell-cell interaction (18).…”

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confidence: 99%

“…Like Notch, the Drosophila neuralized gene (neu) is a neurogenic gene whose function is to limit the number of neuronal precursor cells and to specify sensory organ as well as R8 photoreceptor cell fates (11)(12)(13)(14)(15)(16)(17). Genetic analyses suggest that neuralized interacts with other neurogenic genes, such as the Notch receptor and the Delta ligand for cell-cell interaction (18).…”

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confidence: 99%

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Ruan

Tecott

Jiang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Neurogenic genes in the Notch receptor-mediated signaling pathway play important roles in neuronal cell fate specification as well as neuronal differentiation. The Drosophila neuralized gene is one of the neurogenic genes. We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that the m-neu1 transcript is expressed in differentiated neurons. Mice deficient for m-neu1 are viable and morphologically normal, but exhibit specific defects in olfactory discrimination and hypersensitivity to ethanol. These findings reveal an essential role of m-neu1 in ensuring proper processing of certain information in the adult brain.M any molecular mechanisms controlling neural development and neural function are evolutionarily conserved (1-3). One example is the Notch-mediated cell-cell interaction, a mechanism to mediate signaling between adjacent cells and thereby to specify cell fates in organisms ranging from worms and flies to mammals (4). In a given organism, the Notch signaling mechanism functions in many developmental processes as well as in adult life (5, 6). In the nervous system, the Notch signaling mechanism is involved in neurogenesis (1, 3), neuronal differentiation (2, 6), axon path finding (7,8), and neurite growth (9, 10). The importance of Notch in maintaining normal neuronal function in the adult has been revealed by a number of human neurological syndromes because of defects in Notch signaling (6).Like Notch, the Drosophila neuralized gene (neu) is a neurogenic gene whose function is to limit the number of neuronal precursor cells and to specify sensory organ as well as R8 photoreceptor cell fates (11)(12)(13)(14)(15)(16)(17). Genetic analyses suggest that neuralized interacts with other neurogenic genes, such as the Notch receptor and the Delta ligand for cell-cell interaction (18). Recent studies (15)(16)(17) revealed that neuralized functions cellautonomously to regulate a subset of Notch-dependent processes. How neuralized affects Notch signaling is unknown at present. An interesting possibility is that Neu protein with its C3HC4 RING finger domain functions as an E3 ubiquitin ligase to modulate Notch signaling (15)(16)(17)19).We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that it is expressed in differentiated neurons. We examined its functional role in the nervous system by generating a loss-of-function allele of m-neu1. Whereas the m-neu1 null mutants exhibit normal performance in a number of behavioral tests, including Morris water maze assay for learning and memory, they display specific functional lesions in olfactory discrimination and ethanol effects on motor coordination. These studies identify specific functions of the adult brain that are critically dependent on m-neu1 activity. Materials and MethodsIsolation of a Mouse Neuralized Homolog. A mouse midgestation embryonic cDNA library (Stratagene) was screened with fragments of Drosophila neuralized cDNA as probes. In brief, the duplicated nylon filters containing mouse phage cDNAs were prehybridized...

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“…We also identi®ed a human gene with strong homology to the Drosophila neuralized (D-neu) gene within this region. D-neu belongs to a group of genes associated with neurogenesis in Drosophila, and its loss-of-function mutation was shown to lead to an over-production of primitive neuronal cells (Boulianne et al, 1991;Price et al, 1993). The human homolog of D-neu, designated as hneu, may therefore be a good candidate for the gene involved in the genesis of malignant astrocytoma.…”

Section: Introductionmentioning

confidence: 99%

Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region

et al. 1998

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The Drosophila neuralized gene encodes a C3HC4 zinc finger.

Cited by 45 publications

References 66 publications

neuralized is essential for a subset of Notch pathway-dependent cell fate decisions during Drosophila eye development

neuralized is essential for a subset of Notch pathway-dependent cell fate decisions during Drosophila eye development

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region

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