Biomedical subjects

J M Shulman

Publications and source records attributed to J M Shulman.

5 recordsLinked to original sources

PubMed2001

PAR-1 is required for the maintenance of oocyte fate in Drosophila.

The PAR-1 kinase is required for the posterior localisation of the germline determinants in C. elegans and Drosophila, and localises to the posterior of the zygote and the oocyte in each case. We show that Drosophila PAR-1 is also required much earlier in oogenesis for the selection of one cell in a germline cyst to become the oocyte. Although the initial steps in oocyte determination are delayed, three markers for oocyte identity, the synaptonemal complex, the centrosomes and Orb protein, still become restricted to one cell in mutant clones. However, the centrosomes and Orb protein fail to translocate from the anterior to the posterior cortex of the presumptive oocyte in region 3 of the germarium, and the cell exits meiosis and becomes a nurse cell. Furthermore, markers for the minus ends of the microtubules also fail to move from the anterior to the posterior of the oocyte in mutant clones. Thus, PAR-1 is required for the maintenance of oocyte identity, and plays a role in microtubule-dependent localisation within the oocyte at two stages of oogenesis. Finally, we show that PAR-1 localises on the fusome, and provides a link between the asymmetry of the fusome and the selection of the oocyte.

Animals↗

PubMed2000

The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole.

In C. elegans, the PAR-1 kinase is localized to the posterior of the zygote and is required for anterior-posterior axis formation. Here, we report that a Drosophila PAR-1 homolog localizes to the posterior of the oocyte with oskar mRNA. Furthermore, par-1 mutants show a novel polarity phenotype in which bicoid mRNA accumulates normally at the anterior, but oskar mRNA is redirected to the center of the oocyte, resulting in embryonic patterning defects. These phenotypes arise from a disorganization of the oocyte microtubule cytoskeleton, consistent with reports that mammalian PAR-1 homologs regulate microtubule dynamics. Thus, Drosophila PAR-1 may remodel the oocyte microtubule network to define the posterior as the site for oskar localization. These results identify a molecular parallel between anterior-posterior polarization in Drosophila and C. elegans.

Animals↗

PubMed1999

Pattern formation in single cells.

Single-cell patterning begins with an asymmetric cue that orients the axis of polarity. Despite great diversity in the types of cues, common mechanisms appear to mediate the polarizing response. Rho-family GTPases initially process and reinforce polarity cues by remodelling cortical actin, and these local asymmetries are subsequently propagated to the microtubules, membrane and secretory pathway to generate the final pattern. Homologues of the yeast polarity genes fulfil similar functions in higher eukaryotes, revealing a fundamental conservation in how polarity arises. Unlike yeast, however, more complex eukaryotic cells can manifest multiple axes of polarity, suggesting that additional mechanisms have evolved to generate more elaborate patterns.

Actins↗

PubMed1998

Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.

In Drosophila, planar cell polarity (PCP) signaling is mediated by the receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling also requires Dsh and may utilize DFz2 as a receptor. Using a heterologous system, we show that Dsh is recruited selectively to the membrane by Fz but not DFz2, and this recruitment depends on the DEP domain but not the PDZ domain in Dsh. A mutation in the DEP domain impairs both membrane localization and the function of Dsh in PCP signaling, indicating that translocation is important for function. Further genetic and molecular analyses suggest that conserved domains in Dsh function differently during PCP and Wg signaling, and that divergent intracellular pathways are activated. We propose that Dsh has distinct roles in PCP and Wg signaling. The PCP signal may selectively result in focal Fz activation and asymmetric relocalization of Dsh to the membrane, where Dsh effects cytoskeletal reorganization to orient prehair initiation.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Frizzled signaling and the developmental control of cell polarity.

Within the last three years, Frizzled receptors have risen from obscurity to celebrity status owing to their functional identification as receptors for the ubiquitous family of secreted WNT signaling factors. However, the founding member of the Frizzled family, Drosophila Frizzled (FZ), was cloned almost a decade ago because of its role in regulating cell polarity within the plane of an epithelium. In this review, we consider the role of FZ in this intriguing context. We discuss recent progress towards elucidating mechanisms for the intracellular specification of planar polarity, and further review evidence for models of global polarity regulation at the tissue level. The data suggest that a genetic 'cassette', encoding a set of core signaling components, could pattern hair, bristle and ommatidial planar polarity in Drosophila, and that additional tissue-specific factors might explain the diversity of signal responses. Recently described examples from the nematode and frog suggest that the developmental control of cell polarity by FZ receptors might represent a functionally conserved signaling mechanism.

Animals↗