Tbx6 Regulates Left/Right Patterning in Mouse Embryos through Effects on Nodal Cilia and Perinodal Signaling

Background: The determination of left/right body axis during early embryogenesis sets up a developmental cascade that coordinates the development of the viscera and is essential to the correct placement and alignment of organ systems and vasculature. Defective left-right patterning can lead to congenital cardiac malformations, vascular anomalies and other serious health problems. Here we describe a novel role for the T-box transcription factor gene Tbx6 in left/right body axis determination in the mouse. Results: Embryos lacking Tbx6 show randomized embryo turning and heart looping. Our results point to multiple mechanisms for this effect. First, Dll1, a direct target of Tbx6, is down regulated around the node in Tbx6 mutants and there is a subsequent decrease in nodal signaling, which is required for laterality determination. Secondly, in spite of a lack of expression of Tbx6 in the node, we document a profound effect of the Tbx6 mutation on the morphology and motility of nodal cilia. This results in the loss of asymmetric calcium signaling at the periphery of the node, suggesting that unidirectional nodal flow is disrupted. To carry out these studies, we devised a novel method for direct labeling and live imaging cilia in vivo using a genetically-encoded fluorescent protein fusion that labels tubulin, combined with laser point scanning confocal microscopy for direct visualization of cilia movement. Conclusions: We conclude that the transcription factor gene Tbx6 is essential for correct left/right axis determination in th

The CALM and CALM/AF10 interactor CATS is a marker for proliferation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The CATS protein was recently identified as a novel CALM interacting protein. CATS increases the nuclear and specifically the nucleolar localization of the leukemogenic CALM/AF10 fusion protein. We cloned and characterized the murine Cats gene. Detailed analysis of murine Cats expression during mouse embryogenesis showed an association with rapidly proliferating tissues. interestingly, the Cats transcript is highly expressed in murine hematopoietic cells transformed by CALM/AF10. The CATS protein is highly expressed in leukemia, lymphoma and tumor cell lines but not in non-proliferating T-cells or human peripheral blood lymphocytes. CATS protein levels are cell cycle dependent and it is induced by mitogens, suggesting a role of CATS in the control of cell proliferation and possibly CALM/AF10-mediated leukemogenesis. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.24356367Deutsche Jose Carreras Leukamie-Stiftung e.V. (DJCLS) [F02/02, F05/06]Frauenbeauftragte-LMU, Munich, GermanyFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Genome Research Network (NGFN) grant from the German Ministry of Education and Research (BMBF) [N1KR-S31T15]Deutsche Forschungsgemeinschaft (DFG) [SFB 684, A6]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Deutsche Jose Carreras Leukamie-Stiftung e.V. (DJCLS) [F02/02, F05/06]FAPESP [07/08019-1, 07/54870-5]National Genome Research Network (NGFN) grant from the German Ministry of Education and Research (BMBF) [N1KR-S31T15]Deutsche Forschungsgemeinschaft (DFG) [SFB 684, A6

Regulation of phyllotaxis by polar auxin transport

The regular arrangement of leaves around a plant's stem, called phyllotaxis, has for centuries attracted the attention of philosophers, mathematicians and natural scientists; however, to date, studies of phyllotaxis have been largely theoretical. Leaves and flowers are formed from the shoot apical meristem, triggered by the plant hormone auxin. Auxin is transported through plant tissues by specific cellular influx and efflux carrier proteins. Here we show that proteins involved in auxin transport regulate phyllotaxis. Our data indicate that auxin is transported upwards into the meristem through the epidermis and the outermost meristem cell layer. Existing leaf primordia act as sinks, redistributing auxin and creating its heterogeneous distribution in the meristem. Auxin accumulation occurs only at certain minimal distances from existing primordia, defining the position of future primordia. This model for phyllotaxis accounts for its reiterative nature, as well as its regularity and stability