TY - JOUR TI - Rac/JNK/dub regulates intercellular adhesive dynamics during gut morphogenesis AU - Dush, Michael AU - Nascone-Yoder, Nanette M. T2 - Developmental Biology DA - 2011/8// PY - 2011/8// DO - 10.1016/j.ydbio.2011.05.136 VL - 356 IS - 1 SP - 141 J2 - Developmental Biology LA - en OP - SN - 0012-1606 UR - http://dx.doi.org/10.1016/j.ydbio.2011.05.136 DB - Crossref ER - TY - JOUR TI - Specification of a Foxj1-Dependent Lineage in the Forebrain Is Required for Embryonic-to-Postnatal Transition of Neurogenesis in the Olfactory Bulb AU - Jacquet, Benoit V. AU - Muthusamy, Nagendran AU - Sommerville, Laura J. AU - Xiao, Guanxi AU - Liang, Huixuan AU - Zhang, Yong AU - Holtzman, Michael J. AU - Ghashghaei, H. Troy T2 - JOURNAL OF NEUROSCIENCE AB - Establishment of a neural stem cell niche in the postnatal subependymal zone (SEZ) and the rostral migratory stream (RMS) is required for postnatal and adult neurogenesis in the olfactory bulbs (OB). We report the discovery of a cellular lineage in the SEZ-RMS-OB continuum, the specification of which is dependent on the expression of the forkhead transcription factor Foxj1 in mice. Spatially and temporally restricted Foxj1+ neuronal progenitors emerge during embryonic periods, surge during perinatal development, and are active only for the first few postnatal weeks. We show that the development of the unique Foxj1-derived lineage is dependent on Foxj1 expression and is required for overall postnatal neurogenesis in the OB. Strikingly, the production of neurons from Foxj1+ progenitors significantly declines after the early postnatal weeks, but Foxj1-derived neurons in the OB persist during adult periods. For the first time, our study identifies the time- and region-specific activity of a perinatal progenitor domain that is required for transition and progression of OB neurogenesis from the embryonic-to-postnatal periods. DA - 2011/6/22/ PY - 2011/6/22/ DO - 10.1523/jneurosci.0171-11.2011 VL - 31 IS - 25 SP - 9368-9382 SN - 0270-6474 ER - TY - JOUR TI - Heterotaxin: A TGF-beta Signaling Inhibitor Identified in a Multi-Phenotype Profiling Screen in Xenopus Embryos AU - Dush, Michael K. AU - McIver, Andrew L. AU - Parr, Meredith A. AU - Young, Douglas D. AU - Fisher, Julie AU - Newman, Donna R. AU - Sannes, Philip L. AU - Hauck, Marlene L. AU - Deiters, Alexander AU - Nascone-Yoder, Nanette T2 - CHEMISTRY & BIOLOGY AB - Disruptions of anatomical left-right asymmetry result in life-threatening heterotaxic birth defects in vital organs. We performed a small molecule screen for left-right asymmetry phenotypes in Xenopus embryos and discovered a pyridine analog, heterotaxin, which disrupts both cardiovascular and digestive organ laterality and inhibits TGF-β-dependent left-right asymmetric gene expression. Heterotaxin analogs also perturb vascular development, melanogenesis, cell migration, and adhesion, and indirectly inhibit the phosphorylation of an intracellular mediator of TGF-β signaling. This combined phenotypic profile identifies these compounds as a class of TGF-β signaling inhibitors. Notably, heterotaxin analogs also possess highly desirable antitumor properties, inhibiting epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation in mammalian systems. Our results suggest that assessing multiple organ, tissue, cellular, and molecular parameters in a whole organism context is a valuable strategy for identifying the mechanism of action of bioactive compounds. DA - 2011/2/25/ PY - 2011/2/25/ DO - 10.1016/j.chembiol.2010.12.008 VL - 18 IS - 2 SP - 252-263 SN - 1879-1301 ER -