numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos

Uemura, Tadashi; Shepherd, S; Ackerman, Larry; Jan, Yuh Nung

doi:10.1016/0092-8674(89)90849-0

Cited by 474 publications

(294 citation statements)

References 41 publications

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“…Moreover, DOC-2 is 66% and 50% identical to mDab1 and Drosophila Dab respectively (Figure 1b). This stretch of amino acids has been described by Bork and Morgolis (1995) as a phosphotyrosine interacting domain (PID, also known as PTB domain) which has also been identi®ed in proteins such as Shc in human and mouse (Zhou et al, 1995), and the Numb gene in Drosophila (Uemura et al, 1989).…”

Section: Identi®cation Of the Full-length Doc-2 Cdnamentioning

confidence: 99%

DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer

et al. 1998

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Using RNA ®ngerprinting (RAP) strategy and Northern blot analysis, we identi®ed a di erentially expressed sequence DOC-2 which is detectable in all normal human ovarian surface epithelial (HOSE) cell cultures but not in ovarian cancer cell lines and tissues. Subsequent cloning of DOC-2 from a cDNA library generated from the HOSE cells was carried out using the 3' and 5' RACE approach. A 3268 base pair full length cDNA of DOC-2 was isolated and sequenced. The predicted protein has a length of 770 amino acids. Homology search of all NCBI sequences indicated that the amino acid sequence of DOC-2 shares 93% homology with the mouse p96/ mDab2 phosphoprotein and has a phosphotyrosine interacting domain (PID) and multiple SH3 binding motifs. Chromosomal localization by FISH showed that the DOC-2 gene is located on 5p13. Western blot analysis showed that the 105 kDa DOC-2 protein was down-regulated in all the carcinoma cell lines. In-situ immunohistochemistry performed on normal ovaries, and benign, borderline and invasive ovarian tumor tissues showed down regulation of DOC-2 protein particularly in serous ovarian tumor tissues. When DOC-2 was transfected into the ovarian carcinoma cell line SKOV3, the stable transfectants showed signi®cantly reduced growth rate and ability to form tumors in nude mice. These data suggest that down-regulation of DOC-2 may play an important role in ovarian carcinogenesis.

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Section: Identi®cation Of the Full-length Doc-2 Cdnamentioning

confidence: 99%

DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer

et al. 1998

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“…Asymmetric cell division is a fundamental way of generating cell diversity in metazoans, and Numb is the first identified intrinsic determinant of cell fate; mutation of Numb leads to the loss of most of the sensory neurons in the Drosophila peripheral nervous system [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b

Shao

Liu

et al. 2016

Cell Res

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Numb is an endocytic protein that plays crucial roles in diverse cellular processes such as asymmetric cell division, cell migration and differentiation. However, the molecular mechanism by which Numb regulates endocytic trafficking is poorly understood. Here, we demonstrate that Numb is a docking regulator for homotypic fusion of early endosomes (EEs). Numb depletion causes clustered but unfused EEs, which can be rescued by overexpressing cytosolic Numb 65 and Numb 71 but not plasma membrane-attached Numb 66 or Numb 72. Time-lapse analysis reveals that paired vesicles tend to tether but not fuse with each other in the absence of Numb. We further show that Numb binds to another docking regulator, Mon1b, and is required for the recruitment of cytosolic Mon1b to the EE membrane. Consistent with this, deletion of Mon1b causes similar defects in EE fusion. Our study thus identifies a novel mechanism by which Numb regulates endocytic sorting by mediating EE fusion.

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“…In Drosophila, the numb protein is asymmetrically localized to one daughter cell during mitosis of external sensory organ (ES) precursors (Rhyu et al, 1994) and the CNS MP2 precursor (Spana et al, 1995). In both lineages, numb is necessary and sufficient to specify the cell fate of the cell in which it is observed (Uemura et al, 1989;Rhyu et al, 1994;Spana et al, 1995;this manuscript).…”

Section: Introductionmentioning

confidence: 99%

“…Mutant lines examined were w; pros 14 /TM3-ftz lacZ and pros 17 /TM3 ; numb 1 pr cn Bc/CyO-ftz lacZ (Uemura et al, 1989); and stg 7B e/TM3-ftz lacZ (Jurgens et al, 1984;Cui and Doe, 1995).…”

Section: Drosophila Strainsmentioning

confidence: 99%

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The PROSPERO transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila

1996

Trends in Genetics

285

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Both intrinsic and extrinsic factors are known to regulate sibling cell fate. Here we describe a novel mechanism for the asymmetric localization of a transcription factor to one daughter cell at mitosis. The Drosophila CNS develops from asymmetrically dividing neuroblasts, which give rise to a large neuroblast and a smaller ganglion mother cell (GMC). The prospero gene encodes a transcription factor necessary for proper GMC gene expression. We show that the prospero protein is synthesized in the neuroblast where it is localized to the F-actin cell cortex. At mitosis, prospero is asymmetrically localized to the budding GMC and excluded from the neuroblast. After cytokinesis, prospero is translocated from the GMC cortex into the nucleus. Asymmetric cortical localization of prospero in neuroblasts requires entry into mitosis; it does not depend on numb function. prospero is also observed in cortical crescents in dividing precursors of the peripheral nervous system and adult midgut. The asymmetric cortical localization of prospero at mitosis is a mechanism for rapidly establishing distinct sibling cell fates in the CNS and possibly other tissues.

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numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos

Cited by 474 publications

References 41 publications

DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer

DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer

Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b

The PROSPERO transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila

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