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Ko, C. S.

Publications and source records attributed to Ko, C. S..

4 recordsLinked to original sources

Cell-supracellular structural relations solve the French Flag Problem without graded molecular control

How patterns of cell state emerge across a tissue field is a fundamental question brought into renewed focus by spatial omics tools that map molecular states onto tissue organization. Here, we investigate how a field of limb progenitor mesenchyme transforms into distinct, adjacent cartilage and soft tissue compartments. We find that mesenchymal tissue fields self-organize their own differentiation through co-constitutive relationships between cell and supracellular structures, which produce cell-ECM or cell-cell-based supracellular cues that canalize cartilage or soft tissue cell fate change, respectively. At the tissue level, bifurcation in intrinsically generated supracellular structures guides the specification of tissue compartment size. We find that Wnt secreted from neighboring epithelial tissue influences mesenchymal cell fate and patterning by functioning as a modulator of cell-supracellular structural relations. Taken together, our results provide insight into how mesenchymal self-organization interfaces with epithelial signaling to enable a tissue compartmentalization process that initiates the skeleton.

developmental biology↗

A giant cell enhancer achieves cell-type specificity through activation via TCP and repression by Dof transcription factors

Proper pattern formation relies on the tight coordination of cell fate specification and cell cycle regulation in growing tissues. How this can be organized at enhancers that activate gene expression necessary for differentiation is not well understood. One such example is the patterning of the Arabidopsis thaliana sepal epidermis where giant cell fate specification is associated with the endoreduplication cell cycle. Previously, we identified an enhancer region capable of driving giant cell-specific expression. In this study, we use the giant cell enhancer as a model to understand the regulatory logic that promotes cell-type specific expression. Our dissection of the enhancer revealed that giant cell specificity is achieved primarily through the combination of two elements: an activator and a repressor. TCP transcription factors are involved in activation of non-specific expression throughout the epidermis with higher expression in endoreduplicated giant cells than small cells. Dof transcription factors act via the second element to repress activity of the enhancer and limit expression to giant cells. Thus, we find that cell-type specific expression emerges from the combined activities of two broadly acting enhancer elements.

plant biology↗

Apical Constriction Reversal upon Mitotic Entry Underlies Different Morphogenetic Outcomes of Cell Division

During development, coordinated cell shape changes and cell divisions sculpt tissues. While these individual cell behaviors have been extensively studied, how cell shape changes and cell divisions that occur concurrently in epithelia influence tissue shape is less understood. We addressed this question in two contexts of the early Drosophila embryo: premature cell division during mesoderm invagination, and native ectodermal cell divisions with ectopic activation of apical contractility. Using quantitative live-cell imaging, we demonstrated that mitotic entry reverses apical contractility by interfering with medioapical RhoA signaling. While premature mitotic entry inhibits mesoderm invagination, which relies on apical constriction, mitotic entry in an artificially contractile ectoderm induced ectopic tissue invaginations. Ectopic invaginations resulted from medioapical myosin loss in neighboring mitotic cells. This myosin loss enabled non-mitotic cells to apically constrict through mitotic cell stretching. Thus, the spatial pattern of mitotic entry can differentially regulate tissue shape through signal interference between apical contractility and mitosis.

developmental biology↗

Microtubules stabilize intercellular contractile force transmission during tissue folding

During development, forces transmitted between cells are critical for sculpting epithelial tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change cell shape (e.g., apical constriction), but can also result in force transmission between cells via attachments to adherens junctions. How actomyosin networks maintain attachments to adherens junctions under tension is poorly understood. Here, we discovered that microtubules stabilize actomyosin intercellular attachments in epithelia during Drosophila mesoderm invagination. First, we used live imaging to show a novel arrangement of the microtubule cytoskeleton during apical constriction: medioapical, non-centrosomal Patronin (CAMSAP) foci formed by actomyosin contraction organizes an apical microtubule network. Microtubules were required for mesoderm invagination but were not necessary for apical contractility or adherens junction assembly. Instead, microtubules promoted the stable connection between medioapical actomyosin and adherens junctions. These results define a role for coordination between actin and microtubule cytoskeletal systems in intercellular force transmission and tissue morphogenesis.

developmental biology↗