ORCID IDs: 0000-0003-4414-0649 (H.T.); 0000-0002-9657-8231 (M. Tasaka); 0000-0002-6176-5758 (M.T.M.)During gravitropism, the directional signal of gravity is perceived by gravity-sensing cells called statocytes, leading to asymmetric distribution of auxin in the responding organs. To identify the genes involved in gravity signaling in statocytes, we performed transcriptome analyses of statocyte-deficient Arabidopsis thaliana mutants and found two candidates from the LAZY1 family, AtLAZY1/LAZY1-LIKE1 (LZY1) and AtDRO3/AtNGR1/LZY2. We showed that LZY1, LZY2, and a paralog AtDRO1/AtNGR2/LZY3 are redundantly involved in gravitropism of the inflorescence stem, hypocotyl, and root. Mutations of LZY genes affected early processes in gravity signal transduction without affecting amyloplast sedimentation. Statocyte-specific expression of LZY genes rescued the mutant phenotype, suggesting that LZY genes mediate gravity signaling in statocytes downstream of amyloplast displacement, leading to the generation of asymmetric auxin distribution in gravity-responding organs. We also found that lzy mutations reversed the growth angle of lateral branches and roots. Moreover, expression of the conserved C-terminal region of LZY proteins also reversed the growth direction of primary roots in the lzy mutant background. In lateral root tips of lzy multiple mutants, asymmetric distribution of PIN3 and auxin response were reversed, suggesting that LZY genes regulate the direction of polar auxin transport in response to gravity through the control of asymmetric PIN3 expression in the root cap columella.

The shootin1–cortactin interaction participates in netrin-1–induced F-actin–adhesion coupling and in the promotion of traction forces for axon outgrowth.

Growth cones navigate axonal projection in response to guidance cues. However, it is unclear how they can decide the migratory direction by transducing the local spatial cues into protrusive forces. Here we show that knockout mice of Shootin1 display abnormal projection of the forebrain commissural axons, a phenotype similar to that of the axon guidance molecule netrin-1. Shallow gradients of netrin-1 elicited highly polarized Pak1-mediated phosphorylation of shootin1 within growth cones. We demonstrate that netrin-1–elicited shootin1 phosphorylation increases shootin1 interaction with the cell adhesion molecule L1-CAM; this, in turn, promotes F-actin–adhesion coupling and concomitant generation of forces for growth cone migration. Moreover, the spatially regulated shootin1 phosphorylation within growth cones is required for axon turning induced by netrin-1 gradients. Our study defines a mechano-effector for netrin-1 signaling and demonstrates that shootin1 phosphorylation is a critical readout for netrin-1 gradients that results in a directional mechanoresponse for axon guidance.

SignificanceCell migration directed by substrate-bound chemical cues is called haptotaxis. This study shows that grip and slip between the cell adhesion molecule (CAM) L1-CAM and the adhesive substrates, which occur asymmetrically under the growth cone, direct growth cone migration mediated by laminin. This mechanism is disrupted in a human patient of L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia. These findings provide a conceptual framework for understanding the regulation and dysregulation of cell migration on the bases of force generation.

A 47 year old woman with two isolated lumps in her right breast underwent an excisional biopsy and the histological findings of both lesions revealed fibroadenoma with an in situ lobular carcinoma. Patey's modified radical mastectomy was performed after which careful follow-up was continued. To date, a total 161 cases of carcinoma arising in a fibroadenoma have been reported in the world literature and a review of these literature is given following the case report.