Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered.

Microtubules enable the planar cell polarity of airway cilia.

Background: Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance.

Results: We show that planar cell polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells, a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; nonautonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization.

A novel role for FOXA2 and SHH in organizing midbrain signaling centers.

The floor plate (FP) is a midline signaling center, known to direct ventral cell fates and axon guidance in the neural tube. The recent identification of midbrain FP as a source of dopaminergic neurons has renewed interest in its specification and organization, which remain poorly understood. In this study, we have examined the chick midbrain and spinal FP and show that both can be partitioned into medial (MFP) and lateral (LFP) subdivisions.

Pointing in the right direction: new developments in the field of planar cell polarity.

Planar cell polarity (PCP) is observed in an array of developmental processes that involve collective cell movement and tissue organization, and its disruption can lead to severe developmental defects. Recent studies in flies and vertebrates have identified new functions for PCP as well as new signalling components, and have proposed new mechanistic models. However, despite this progress, the search to simplify principles of understanding continues and important mechanistic uncertainties still pose formidable challenges.

Diversification of the expression patterns and developmental functions of the dishevelled gene family during chordate evolution.

Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice. Moreover, we find that the expression patterns of Dvl genes in the chick diverge significantly from those of Xenopus.

Regulation of ventral midbrain patterning by Hedgehog signaling.

In the developing ventral midbrain, the signaling molecule sonic hedgehog (SHH) is sufficient to specify a striped pattern of cell fates (midbrain arcs). Here, we asked whether and precisely how hedgehog (HH) signaling might be necessary for ventral midbrain patterning. By blocking HH signaling by in ovo misexpression of Ptc1(Delta)(loop2), we show that HH signaling is necessary and can act directly at a distance to specify midbrain cell fates.