Biomedical subjects

A Bashirullah

Publications and source records attributed to A Bashirullah.

5 recordsLinked to original sources

PubMed1999

Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.

Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein-protein interaction domains: a phosphotyrosine-binding domain and a proline-rich region (PRR) that functions as an SH3-binding domain. Here we show that there are at least four human NUMB isoforms and that these serve two distinct developmental functions in the neuronal lineage: differentiation (but not proliferation) is promoted by human NUMB protein isoforms with a type I (short) PRR. In contrast, proliferation (but not differentiation) is directed by isoforms that have a type II (long) PRR. The two types of PRR may promote distinct intracellular signaling pathways downstream of the NOTCH receptor during mammalian neurogenesis.

Alternative Splicing↗

PubMed1999

Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.

Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT.

3' Untranslated Regions↗

PubMed1998

RNA localization in development.

Cytoplasmic RNA localization is an evolutionarily ancient mechanism for producing cellular asymmetries. This review considers RNA localization in the context of animal development. Both mRNAs and non-protein-coding RNAs are localized in Drosophila, Xenopus, ascidian, zebrafish, and echinoderm oocytes and embryos, as well as in a variety of developing and differentiated polarized cells from yeast to mammals. Mechanisms used to transport and anchor RNAs in the cytoplasm include vectorial transport out of the nucleus, directed cytoplasmic transport in association with the cytoskeleton, and local entrapment at particular cytoplasmic sites. The majority of localized RNAs are targeted to particular cytoplasmic regions by cis-acting RNA elements; in mRNAs these are almost always in the 3'-untranslated region (UTR). A variety of trans-acting factors--many of them RNA-binding proteins--function in localization. Developmental functions of RNA localization have been defined in Xenopus, Drosophila, and Saccharomyces cerevisiae. In Drosophila, localized RNAs program the antero-posterior and dorso-ventral axes of the oocyte and embryo. In Xenopus, localized RNAs may function in mesoderm induction as well as in dorso-ventral axis specification. Localized RNAs also program asymmetric cell fates during Drosophila neurogenesis and yeast budding.

Animals↗

PubMed1997

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases. Thus fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.

Amino Acid Sequence↗

PubMed1996

Mammalian NUMB is an evolutionarily conserved signaling adapter protein that specifies cell fate.

BACKGROUND: Drosophila numb was originally described as a mutation affecting binary divisions in the sensory organ precursor (SOP) lineage. The numb gene was subsequently shown to encode an asymmetrically localized protein which is required for binary cell-fate decisions during peripheral nervous system development. Part of the Drosophila NUMB protein exhibits homology to the SHC phosphotyrosine-binding (PTB) domain, suggesting a potential link to tyrosine-kinase signal transduction. RESULTS: A widely expressed mammalian homologue of Drosophila numb (dnumb) has been cloned from rat and is referred to here as mammalian Numb (mNumb). The mNUMB protein has a similar overall structure to dNUMB and 67 sequence similarity. Misexpression of mNumb in Drosophila during sensory nervous system precursor cell division causes identical cell fate transformations to those produced by ectopic dNUMB expression. In vitro, the mNUMB PTB domain binds phosphotyrosine-containing proteins, and SH3 domains of SRC-family tyrosine kinases bind to mNUMB presumably through interactions with proline-rich regions in the carboxyl terminus. Overexpression of full-length mNUMB in the multipotential neural crest stem cell line MONC-1 dramatically biases its differentiation towards neurons, whereas overexpression of the mNUMB PTB domain biases its differentiation away from neuronal fates. CONCLUSIONS: Our results demonstrate that mNUMB is an evolutionarily conserved functional homologue of dNUMB, and establish a link to tyrosine-kinase-mediated signal transduction pathways. Furthermore, our results suggest that mNUMB and dNUMB are new members of a family of signaling adapter molecules that mediate conserved cell-fate decisions during development.

Amino Acid Sequence↗