Asexual animals and plants are usually polyploid, and polyploid animals (and triploid plants) are often asexual (Astaurov 1969;Bierzychudek 1985;Suomalainen 1987;Otto and Whitton 2000). Why polyploidy and asexuality are associated, however, remains unclear (Gregory 2005). To complicate matters, there is growing evidence that ploidy level within presumed obligate asexual lineages is surprisingly variable and complex (Lynch 1984;Belshaw et al. 1999;Castagnone-Sereno 2006). Independent origin of asexual lineages from sexuals that themselves vary in karyotype or genome size and occasional fertilization of otherwise asexual individuals are the two most commonly suggested causes for this complexity, especially when ploidy elevation is involved (e.g., amphibians: Bogart and

The APC tumor suppressor regulates diverse stem cell processes including gene regulation through Wnt-b-catenin signaling and chromosome stability through microtubule interactions, but how the disparate functions of APC are controlled is not well understood. Acting as part of a Wnt-b-catenin pathway that controls asymmetric cell division, Caenorhabditis elegans APC, APR-1, promotes asymmetric nuclear export of the b-catenin WRM-1 by asymmetrically stabilizing microtubules. Wnt function also depends on a second b-catenin, SYS-1, which binds to the C. elegans TCF POP-1 to activate gene expression. Here, we show that APR-1 regulates SYS-1 levels in asymmetric stem cell division, in addition to its known role in lowering nuclear levels of WRM-1. We demonstrate that SYS-1 is also negatively regulated by the C. elegans homolog of casein kinase 1a (CKIa), . We show that KIN-19 restricts APR-1 localization, thereby regulating nuclear WRM-1. Finally, the polarity of APR-1 cortical localization is controlled by PRY-1 (C. elegans Axin), such that PRY-1 controls the polarity of both SYS-1 and WRM-1 asymmetries. We propose a model whereby Wnt signaling, through CKIa, regulates the function of two distinct pools of APC -one APC pool negatively regulates SYS-1, whereas the second pool stabilizes microtubules and promotes WRM-1 nuclear export.

Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure. This new analytical approach elucidates several differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3 and demonstrates the ability of tissue-level imaging and analysis to generate cell-biological mechanistic insights into neural tube closure.

Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure This approach elucidates new differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3 and demonstrates the ability of tissue-level imaging and analysis to generate cell-biological mechanistic insights into neural tube closure.

The Wnt/β-catenin signaling pathway is utilized across metazoans. However, the mechanism of signal transduction, especially dissociation of the β-catenin destruction complex by Dishevelled proteins, remains controversial. Here, we describe the function of the Dishevelled paralogs DSH-2 and MIG-5 in the Wnt/β-catenin asymmetry (WβA) pathway in Caenorhabditis elegans, where WβA drives asymmetric cell divisions throughout development. We find that DSH-2 and MIG-5 redundantly regulate cell fate in hypodermal seam cells. Similarly, both DSH-2 and MIG-5 are required for positive regulation of SYS-1 (a C. elegans β-catenin), but MIG-5 has a stronger effect on the polarity of SYS-1 localization. We show that MIG-5 controls cortical APR-1 (the C. elegans APC) localization. DSH-2 and MIG-5 both regulate the localization of WRM-1 (another C. elegans β-catenin), acting together as negative regulators of WRM-1 nuclear localization. Finally, we demonstrate that overexpression of DSH-2 or MIG-5 in seam cells leads to stabilization of SYS-1 in the anterior seam daughter, solidifying the Dishevelled proteins as positive regulators of SYS-1. Overall, we have further defined the role of Dishevelled in the WβA signaling pathway, and demonstrated that DSH-2 and MIG-5 regulate cell fate, β-catenin nuclear levels and the polarity of β-catenin regulation.