Biology subjects

Goins, L. M.

Publications and source records attributed to Goins, L. M..

4 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2023

Wnt signaling couples G2 phase control with differentiation during hematopoiesis

During homeostasis, a critical balance is maintained between myeloid-like progenitors and their differentiated progeny, which function to mitigate stress and innate immune challenges. The molecular mechanisms that help achieve this balance are not fully understood. Using genetic dissection in Drosophila, we show that a Wnt6/EGFR-signaling network simultaneously controls progenitor growth, proliferation, and differentiation. Unlike G1-quiescence of stem cells, hematopoietic progenitors are blocked in the G2 phase by a {beta}-catenin-independent Wnt6 pathway that restricts Cdc25 nuclear entry and promotes cell growth. Canonical {beta}-catenin-dependent Wnt6 signaling is spatially confined to mature progenitors through localized activation of the tyrosine-kinases EGFR and Abl, which promote nuclear entry of {beta}-catenin and facilitate exit from G2. This strategy combines transcription-dependent and - independent forms of both Wnt6 and EGFR pathways to create a direct link between cell-cycle control and differentiation. This unique combinatorial strategy employing conserved components may underlie homeostatic balance and stress response in mammalian hematopoiesis.

developmental biology↗

bioRxiv2021

Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis

Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, while inhibiting canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.

developmental biology↗

bioRxiv2020

Intermediate Progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants

Genetic and genomic analysis in Drosophila suggests that hematopoietic progenitors likely transition into terminal fates via intermediate progenitors (IPs) with some characteristics of either, but perhaps maintaining IP-specific markers. In the past, IPs have not been directly visualized and investigated due to lack of appropriate genetic tools. Here we report a split-GAL4 construct, CHIZ-GAL4, that identifies IPs as cells physically juxtaposed between true progenitors and differentiating hemocytes. IPs comprise a distinct cell type with a unique cell-cycle profile and they remain multipotent for all blood cell fates. Additionally, through their dynamic control of the Notch ligand, Serrate, IPs specify the fate of direct neighbors. The Ras pathway controls the number of IP cells and promotes their transition into differentiating cells. The split-GAL4 strategy is amenable for adoption in mammalian systems and would be invaluable in assigning trajectories that stem and progenitor populations follow as they develop into mature blood cells.

developmental biology↗