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Riggs, B.

Publications and source records attributed to Riggs, B..

4 recordsLinked to original sources

miR-190 is a Key Regulator in Establishing Cell Polarity and Specification in the Drosophila Nervous System

Asymmetric cell division generates cellular diversity in developing tissues, particularly in the CNS. In Drosophila neuroblasts, this process relies on polarity complexes and fate determinants, yet its molecular regulation remains unclear. Here, we identify miRNA-190 as a key regulator of neuroblast polarity and differentiation. Single-cell RNA sequencing and transcriptome analysis reveal that miR-190 deficiency disrupts CNS cell populations, reducing neurons while increasing neural progenitors and glia. Mechanistically, miR-190 is required for proper localization of the Par complex and basal determinants during mitosis. In miR-190 mutants, these factors mislocalize, leading to defective polarity and fate specification in embryonic neuroblast. qPCR analysis shows that miR-190 targets RhoGAP, which modulates Cdc42 activation and Par-6, crucial factors in neuroblast polarity. We propose a model in which miR-190 ensures proper Cdc42 activation and polarity establishment by targeting transcripts for degradation. miR-190 has been implicated in various cancers, and our findings provide a mechanistic framework for understanding miR-190s roles in tumorigenesis and its broader involvement in metabolic diseases.

cell biology↗

Undergraduate GPA does not predict success in PhD programs for cohorts of MS students at two minority-serving institutions

Master of Science (MS) research training programs funded by organizations such as the NIH, the NSF as well as private corporations represent the potential for significant interventions for student success, especially for marginalized or underrepresented and first-generation students, to bridge the gap between undergraduate studies and doctoral programs. These students often face serious challenges during their undergraduate years, such as navigating unfamiliar academic systems, balancing demanding coursework with work responsibilities, and fulfilling family obligations. These and other systemic pressures can impede their academic progress and opportunities for research experience. We therefore asked how their undergraduate GPA impacted success in the PhD in terms of (i) acceptance, (ii) completion, and (iii) time to degree after participating in a funded MS research training program. We examined data collected at San Francisco State University and California State University, Los Angeles over a 30-year period because they (i) had similar student demographics, (ii) were institutions with strong MS degrees, and (iii) had an infrastructure (established offices) to coordinate various training programs. We found that high GPA did not predict greater success in entering or completing the PhD, or in time to degree. This study, therefore, demonstrates that undergraduates from diverse groups with lower undergraduate GPA levels can benefit from a structured MS research training program in reaching their goal of becoming a PhD scientist. Moreover, it indicates that more holistic approaches in admissions are required, including limiting the use of a GPA below 3.0 as an early filter to eliminate applicants. These MS programs appear to play a crucial role as a bridge to PhD studies and are instrumental in enhancing diversity within STEM fields. We suggest that a strategy for success is to provide infrastructure in the form of a coordinated office housing the training grants as a means of structuring mentorship and professional development for under-represented and first generation students.

scientific communication and education↗

A deficiency screen of the 3rd chromosome for dominant modifiers of the Drosophila ER integral membrane protein, Jagunal

The mechanism surrounding chromosome inheritance during cell division has been well documented, however, organelle inheritance during mitosis is less understood. Recently, the Endoplasmic Reticulum (ER) has been shown to reorganize during mitosis, dividing asymmetrically in proneuronal cells prior to cell fate selection, indicating a programmed mechanism of inheritance. ER asymmetric partitioning in proneural cells relies on the highly conserved ER integral membrane protein, Jagunal (Jagn). Knockdown of Jagn in the compound Drosophila eye displays a pleotropic rough eye phenotype in 48% of the progeny. To identify genes involved in Jagn dependent ER partitioning pathway, we performed a dominant modifier screen of the 3rd chromosome for enhancers and suppressors of this Jagn RNAi-induced rough eye phenotype. We screened through 181 deficiency lines covering the 3L and 3R chromosomes and identified 12 suppressors and 10 enhancers of the Jagn RNAi phenotype. Based on the functions of the genes covered by the deficiencies, we identified genes that displayed a suppression or enhancement of the Jagn RNAi phenotype. These include Division Abnormally Delayed (Dally), an heparan sulfate proteoglycan, the {gamma}-secretase subunit Presenilin, and the ER resident protein Sec63. Based on our understanding of the function of these targets, there is a connection between Jagn and the Notch signaling pathway. Further studies will elucidate the role of Jagn and identified interactors within the mechanisms of ER partitioning during mitosis.

genetics↗

Microtubules are necessary for proper Reticulon localization during mitosis

During mitosis, the structure of the Endoplasmic Reticulum (ER) displays a dramatic reorganization and remodeling event, however the mechanism driving these changes is poorly understood. Recently, the Reticulon family of ER shaping proteins has been identified as possible factors to promote these drastic changes in ER morphology. In addition, the Reticulons and other ER shaping proteins have been directly linked to several hereditary neurodegenerative disorders. Here, we provide key insight into the cytoskeletal factors involved in the Drosophila Reticulon, Reticulon-like 1 (Rtnl1) during mitosis in the early embryo. At prometaphase, Rtnl1 localizes at the spindle poles just prior to the bulk of ER localization suggesting a role in recruitment. Using precise temporal injections of cytoskeletal inhibitors in the early syncytial Drosophila embryo, we show that microtubules, not microfilaments are necessary for proper Rtnl1 localization and function during mitosis. Lastly, we show that astral microtubules are necessary for Rtnl1 localization at the spindle poles early in mitosis. This work highlights the role of the microtubule cytoskeleton in Rtnl1 localization and ER dynamics during mitosis and sheds light on a pathway towards inheritance of this major organelle.

cell biology↗