稲木 美紀子

Abstract Eukaryotic cells possess intrinsic chirality in their structure, motility, and intracellular dynamics, which are designated cell chirality. Cell chirality participates in the left–right asymmetric morphogenesis and tissue integrity. However, the mechanisms of cell chirality formation remain elusive. InDrosophila, two evolutionarily conserved myosin I genes,Myosin 1D(Myo1D) andMyosin 1C (Myo1C), respectively, dictate the dextral and sinistral chirality of the cells and body. Here, we reported that Myo1D and Myo1C respectively directed the clockwise and counterclockwise circumferential flow of F-actin inDrosophilamacrophages. Both induced the corresponding circular cytoplasm flows and depended on Myosin2 (Myo2). In a modifiedin vitromotility assay using near-physiological actin concentrations, Myo1D triggered the self-organization of the F-actin ring (chiral F-actin ring) that rotated clockwise; conversely, Myo1C induced the random flow of F-actin. The chiral F-actin ring implied that the F-actin bundle was parallelly and annularly polarized concerning its barbed pointed end. Considering that Myo1D and Myo1C are localized to the dorsal plasma membrane of macrophages, Myo1D and Myo1C might organize the parallelly polarized F-actin in macrophages. Our results suggest that Myo2 might drive the clockwise circumferential flow of F-actin along its parallel and annular polarity induced by Myo1D, which may be a molecular basis of cell and organ chirality.

Complex organ structures are formed with high reproducibility. To achieve such intricate morphologies, the responsible epithelium undergoes multiple simultaneous shape changes, such as elongation and folding. However, these changes have typically been assessed separately. In this study, we revealed how distinct shape changes are controlled during internal organ morphogenesis. The Drosophila embryonic hindgut undergoes left-right asymmetric rotation and anteroposterior elongation in a tissue-autonomous manner driven by cell sliding and convergent extension, respectively, in the hindgut epithelia. However, the regulation of these processes remains unclear. Through genetic analysis and live imaging, we demonstrated that cell sliding and convergent extension are independently regulated by Myosin1D and E-cadherin, and Par-3, respectively, whereas both require MyosinII activity. Using a mathematical model, we demonstrated that independently regulated cellular dynamics can simultaneously cause shape changes in a single mechanical system using anisotropic edge contraction. Our findings indicate that distinct cellular dynamics sharing a common apparatus can be independently and simultaneously controlled to form complex organ shapes. This suggests that such a mechanism may be a general strategy during complex tissue morphogenesis.

The role of Drosophila numb in regulating Notch signaling and neurogenesis has been extensively studied, with a particular focus on its effects on the peripheral nervous system (PNS). Previous studies based on a single loss-of-function allele of numb, numb1, showed an antineurogenic effect on the peripheral nervous system (PNS), which revealed that the wild-type numb suppresses Notch signaling. In the current study, we examined whether this phenotype is consistently observed in loss-of-function mutations of numb. Two more numb alleles, numbEY03840 and numbEY03852, were shown to have an antineurogenic phenotype in the PNS. We also found that introducing a wild-type numb genomic fragment into numb1 homozygotes rescued their antineurogenic phenotype. These results demonstrated that loss-of-function mutations of numb universally induce this phenotype. Many components of Notch signaling are encoded by maternal effect genes, but no maternal effect of numb was observed in this study. The antineurogenic phenotype of numb was found to be dependent on the Enhancer of split (E(spl)), a downstream gene of Notch signaling. We found that the combination of E(spl) homozygous and numb1 homozygous suppressed the neurogenic phenotype of the embryonic central nervous system (CNS) associated with the E(spl) mutation. In the E(spl) allele, genes encoding basic helix-loop-helix proteins, such as m5, m6, m7, and m8, remain. Thus, in the E(spl) allele, derepression of Notch activity by numb mutation can rescue the neurogenic phenotype by increasing the expression of the remaining genes in the E(spl) complex. We also uncovered a role for numb in regulating neuronal projections. Our results further support an important role for numb in the suppression of Notch signaling during embryonic nervous system development.