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The serine--threonine kinase LKB1 regulates cell polarity from Caenorhabditis elegans to man. Loss of Ikb1 leads to a cancer predisposition, known as Peutz--Jeghers Syndrome. Biochemical analysis indicates that LKB1 can phosphorylate and activate a family of AMPK-like kinases, however, the precise contribution of these kinases to the establishment and maintenance of cell polarity is still unclear. Recent studies propose that LKB1 acts primarily through the AMP kinase to establish and/or maintain cell polarity. To determine whether this simple model of how LKB1 regulates cell polarity has relevance to complex tissues, we examined Ikb1 mutants in the Drosophila eye. We show that adherens junctions expand and apical, junctional, and basolateral domains mix in Ikb1 mutants. Surprisingly, we find LKB1 does not act primarily through AMPK to regulate cell polarity in the retina. Unlike Ikb1 mutants, ampk retinas do not show elongated rhabdomeres or expansion of apical and junctional markers into the basolateral domain. In addition, nutrient deprivation does not reveal a more dramatic polarity phenotype in Ikb1 photoreceptors. These data suggest that AMPK is not the primary target of LKB1 during eye development. Instead, we find that a number of other AMPK-like kinase, such as SIK, NUAK, Par-1, KP78a, and KP78b show phenotypes similar to weak Ikb1 loss of function in the eye. These data suggest that in complex tissues, LKB1 acts on an array of targets to regulate cell polarity. AMPK | SIK | NUAK | Par-1 | KP78

Iroquois transcription factors regulate diverse aspects of developmental patterning in all metazoans. Despite their widespread importance, the direct targets of the Iroquois are poorly understood. Here, we use in vitro site selection to define the DNA-binding preference of the Drosophila Iroquois Mirror. We use electrophoretic mobility shift assays to determine the critical nucleotides for Mirror binding and to show that this site is recognized by other Drosophila Iroquois transcription factors. This site also is recognized by vertebrate Iroquois transcription factors. Transgenic analysis demonstrates that Drosophila Iroquois proteins recognize this site in vivo to mediate transcriptional repression. We further show that Iroquois transcription factors form homodimers and heterodimers, suggesting that combinatorial binding may contribute to gene regulation by this family. development | Drosophila | Notch | planar polarity | fringe

How did cells of early metazoan organisms first organize themselves to form a body axis? The canonical Wnt pathway has been shown to be sufficient for induction of axis in Cnidaria, a sister group to Bilateria, and is important in bilaterian axis formation. Here, we provide experimental evidence that in cnidarian Hydra the Hippo pathway regulates the formation of a new axis during budding upstream of the Wnt pathway. The transcriptional target of the Hippo pathway, the transcriptional coactivator YAP, inhibits the initiation of budding in Hydra and is regulated by Hydra LATS. In addition, we show functions of the Hippo pathway in regulation of actin organization and cell proliferation in Hydra. We hypothesize that the Hippo pathway served as a link between continuous cell division, cell density, and axis formation early in metazoan evolution. [ABSTRACT FROM AUTHOR]

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in Hydra, a member of phylum Cnidaria a sister group of bilaterian. We found Hydra does not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell– cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization. [ABSTRACT FROM AUTHOR]