Development最新文献

Heterogeneity and complexity of cytoskeletal structures, and how these are regulated, is poorly understood. Here, we use cells of the Drosophila pupal eye as models to explore diversity in the actin cytoskeleton. We found that different F-actin structures emerge in primary, secondary and tertiary pigment cells as they mature. Primary cells became characterized by dense accumulations of F-actin that we termed apical ribs of actin fibers (ARAFs). The formins Diaphanous and Dishevelled Associated Activator of Morphogenesis are essential for generation of ARAFs, which are connected into a network by α-Actinin, the villin Quail, and spectrins, and linked to the apical membrane by Quail and spectrins. ARAFs are similar to stress fibers and connect to adherens junctions. Impairing ARAFs indicated that this network maintains cortical tension and is crucial for primary cells to achieve their characteristic shapes. Our evaluation of the three-dimensional shape of primary cells revealed that ARAFs are essential for the shape of the curved apical membrane. Hence, a toolkit of conserved actin regulatory proteins builds and maintains a network of apical stress fibers that governs the morphology of primary cells.

Chronologically inappropriate morphogenesis (chinmo) has been implicated as a potential juvenile stage specifier gene in Drosophila melanogaster. In their work, Yui Suzuki and Hana Nagata investigate the developmental role of chinmo in another hemimetabolous species, the large milkweed bug Oncopeltus fasciatus. To learn about their work, we spoke to the first author, Hana Nagata, and the corresponding author, Yui Suzuki, Dorothy and Charles Jenkins, Jr. Distinguished Chair in Science and Professor of Biological Sciences, Wellesley College, USA.

Stem cells require signals from a cellular microenvironment known as the niche that regulates identity, location and division of stem cells. Niche cell identity must be properly specified during development to form a tissue capable of functioning in the adult. Here, we show that the Tbx1 ortholog org-1 is expressed in Drosophila testis niche cells in response to Slit and FGF signals. org-1 is expressed during niche development and is required to specify niche cell identity. org-1 mutants specified fewer niche cells, and those cells showed disruption of niche-specific markers, including loss of the niche adhesion protein Fas3 and reduced hedgehog expression. We found that org-1 expression in somatic gonadal precursors is capable of inducing formation of additional niche cells. Disrupted niche identity in org-1 mutants caused defects in niche assembly and functionality. We found that the conserved transcription factor islet is expressed in response to org-1 and show that islet functions downstream to mediate niche identity and assembly. This work identifies a previously unreported role for org-1 in niche establishment.

To generate haploid gametes, germ cells must transition from mitosis to meiosis. In mammals, the transcriptional activator STRA8-MEIOSIN mediates the decision to enter the meiotic cell cycle, but how germ cells prevent continued mitotic cycling before meiotic entry remains unclear. MEIOC was previously shown to repress the mitotic program after meiotic entry. Here, we investigate the role of MEIOC in the mitosis-to-meiosis transition during mouse oogenesis. Using cell proliferation analysis and cell cycle transcriptomics, we demonstrate that MEIOC prevents continued mitotic cycling prior to meiotic entry in oogenic cells. We find that G1/S cyclin CCNA2 is downregulated during the mitosis-to-meiosis transition, and MEIOC contributes to this downregulation. MEIOC also promotes entry into meiosis by increasing Meiosin transcript abundance and consequently activating STRA8-MEIOSIN. Thus, in mouse oogenic cells, the transition from mitosis to meiosis occurs as two molecularly regulated steps - (1) the halt of mitotic cycling and (2) entry into the meiotic cell cycle - and that MEIOC modifies the cell cycle program to facilitate both steps in this transition.

The Foxd1+ stromal progenitor cells give rise to the majority of the renal interstitium; yet, much remains to be understood about how this self-renewing progenitor population is regulated during development. Here, we demonstrate that disruption of the nephron progenitor cell (NPC) lineage via loss of Wt1 (i.e. Six2cre;Wt1c/c) results in an expansion of Foxd1+ progenitor cells in mice. Analyses of two additional models (i.e. Wnt4-null mutants, which fail to form nephron structures similar to Six2cre;Wt1c/c kidneys, and NPC ablation via diphtheria toxin using the Six2cre;RosaDTAc/+) phenocopy the expansion in Foxd1+ cells and further confirm that mutant kidneys with defects in nephrogenesis develop an abnormal increase in the stromal progenitor population. Furthermore, single nuclei RNA-sequencing shows transcriptional changes in the Foxd1+ progenitor cells from Six2cre;Wt1c/c kidneys and identifies a distinct subcluster of the Foxd1+ stroma, which is maintained independent of signals from the nephrogenic niche in the Six2cre;RosaDTAc/+ model. Overall, these findings provide insights into the developmental regulation of the stromal progenitor population and uncover heterogeneity within the Foxd1+ cells, which undergo both cellular and molecular changes in response to defects in nephrogenesis.

Plants continuously produce lateral organs, such as leaves and flowers, from the shoot apical meristem (SAM). This process is guided by the accumulation of the plant hormone auxin and the polar localization of the efflux protein PIN-FORMED1 (PIN1). The transcription factor MONOPTEROS (MP) plays a crucial role in orienting PIN1 polarity, thereby facilitating auxin-driven organogenesis. In this study, we investigate genes downstream of MP that may regulate PIN1 polarity and organogenesis, discovering that the downstream vascular transcription factor TMO5 can promote PIN1 polarity convergence non-cell-autonomously and that TMO5 and its family members promote organ initiation in the SAM. By examining the role of auxin and cytokinin downstream of these genes, we provide evidence that the TMO5-like genes control PIN1 polarity and drive organogenesis by coordinating multiple hormonal signalling pathways.

Hedgehog (HH) signalling is crucial for nervous system patterning. Genetic variants in key HH regulators, such as Gpr161, have been clinically linked to cranial neural tube closure defects (exencephaly) - a congenitally lethal condition. However, the role of Gpr161 in cranial neural tube closure remains unclear. In their latest study, Eric Brooks, Saikat Mukhopadhyay and colleagues present a substantial advance to our understanding of HH pathway logic across the developing murine nervous system by showing that ciliary GPR161 regulates HH signalling in different ways along the neural tube, with different consequences for cell remodelling and tube-closure. To learn more about this work and the people behind it, we talked to first author Sun-Hee Hwang, corresponding author Saikat Mukhopadhyay, and both first and corresponding author Eric Brooks.

The capacity to detect and respond to injury is crucial for the recovery and long-term survival of many organisms. Wnts are commonly induced by tissue damage but how they become activated transcriptionally is not well understood. Here, we report that mouse Wnt1 and Wnt10b are induced following injury in both lung and muscle. These Wnts occupy the same chromosome and are transcribed in opposite directions with 12 kb between them. We identified a highly conserved cis-acting regulatory region (enhancer) residing between Wnt1 and Wnt10b that, when fused to a lacZ reporter, is activated post-injury. This enhancer harbors putative AP-1-binding sites that are required for reporter activity, a feature observed in other injury-responsive enhancers. Injured muscles in mice carrying a germline deletion of the enhancer region display reduced Wnt1 and Wnt10b expression and show elevated intramuscular adipogenesis, which can be a hallmark of impaired muscle regeneration or tissue maintenance. Enhancer redundancy is common in development, but our in vivo analysis shows that loss of a single injury-responsive regulatory region in adult tissues can produce a detectable phenotype.

Cell fusion is a fundamental process in the development of many multicellular organisms, but its precise role in gene regulation and differentiation remains largely unknown. The Caenorhabditis elegans epidermis, which comprises multiple syncytial cells in the adult, represents a powerful model for studying cell fusion in the context of animal development. The largest of these epidermal syncytia, hyp7, integrates 139 individual nuclei through processive cell fusion mediated by the fusogenic protein EFF-1. To explore the role of cell fusion in developmental progression and associated gene expression changes, we conducted transcriptomic analyses of eff-1 fusion-defective C. elegans mutants. Our RNA-seq findings showed widespread transcriptomic changes including the enrichment of epidermal genes and molecular pathways involved in epidermal function during development. Single-molecule fluorescence in situ hybridization further validated the observed altered expression of mRNA transcripts. Moreover, bioinformatic analysis suggests that fusion may play a key role in promoting developmental progression within the epidermis. Our results underscore the significance of cell-cell fusion in shaping transcriptional programs during development.