Intrinsic Polarity Research Articles

The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea.

Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC), a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

Bi2O2(OH)(NO3) as a desirable [Bi2O2]2+layered photocatalyst: strong intrinsic polarity, rational band structure and {001} active facets co-beneficial for robust photooxidation capability

Non-centrosymmetric polar Bi2O2(OH)(NO3) with a rational band structure and {001} active exposing facets is developed as a robust layered photocatalyst for photooxidative diverse industrial contaminants and pharmaceuticals.

Cell memory and adaptation in chemotaxis.

How cells direct motion in response to environmental stimuli has long fascinated biologists. Chemotaxis, the migration guided by chemical gradients, is a fundamental property of many cells and plays important roles in physiology and pathological conditions. One of the best-studied models for chemotaxis is the social amoeba Dictyostelium discoideum. In nutrient-deprived environments, Dictyostelium cells initiate a developmental program that allows them to aggregate and form fruiting bodies. During this process, cells periodically secrete cAMP, which functions as a chemoattractant to guide their migration. In a field of cells, periodic waves of cAMP are initiated from an aggregation center every ∼6 min and sweep out in concentric circles or spirals. As the waves approach cells, they first experience a spatial gradient, with the high side facing the center. Thereafter, because the spatial profile of the waves is symmetric (1), as the peak of the wave passes cells are faced with an equivalent but oppositely directed gradient (Fig. 1). Despite this change of direction, the overall movement of cells is toward the center. How chemotactic cells are able to sense the approaching wave but appear to ignore it as it moves away is known as the “back of the wave” problem, and has perplexed the field for some time. Two possible explanations have been proposed. The first explanation relies on the fact that cells adapt—or cease to respond—to constant levels of stimuli (2). Therefore, cells are more sensitive during the rising phase of the wave, when the concentration of the chemoattractant is increasing over time, and lose sensitivity at the back of the wave when the concentration is declining. The second explanation notes that over time cells develop an intrinsic polarity with well-defined anterior and posterior regions, and this polarity allows cells to maintain their direction when the guidance cue fluctuates (3). The relative importance of each process in allowing cells to move unidirectionally in periodic waves has not been known, although both suggest that in addition to the spatial profile, cells make use of the temporal information of the concentration. In PNAS, Skoge et al. address this question through careful analysis of migration and the corresponding signaling activities of cells responding to spatiotemporal patterns of cAMP generated by a novel microfluidic device (4). The authors show that cells display a memory that persists beyond—but is modulated by—the adaptation process. This interplay between memory and adaptation allows cells to move against the gradient in the back of the wave.

A function for the midbody remnant in embryonic patterning

Asymmetric cell divisions combine cell division with fate specification and one general model of how this is achieved was proposed already decades ago1,2: During interphase, the cell polarity axis is specified, followed by orientation of the spindle along the polarity axis and segregation of fate determinants along the polarity axis during mitosis. In most cells, the polarity axis and the spindle will usually align with the long axis that the cell had before division, also called Hertwig’s rule3–6. In the C. elegans embryo, the first polarity axis also forms along the long axis of the embryo by enrichment of myosin in the anterior7 and formation of mutually exclusive anterior and posterior cortical polarity domains, mediated through directional cortical contractile flow8–10. The directionality of this flow is determined by an extrinsic cue, the entry of the sperm, which inhibits Rho-dependent myosin activation at the future posterior pole by bringing with it the Rho GTPase activating protein CYK-411,12. Moreover, since there is no previous division ‘history’ before the first cleavage, mechanisms have to ensure that the nucleus-centrosome complex undergoes a 90 degree rotation so that the spindle can subsequently elongate along the long axis13–15. Additional mechanisms ensure that the site of cleavage is perpendicular to the long axis16,17. Hence, tight coupling of an extrinsic cue to intrinsic polarity formation and spindle elongation enables alignment of the division orientation with the long axis of the organism and successful segregation of fate determinants.

Allocentric visual cues influence mental transformation of bodies

Identifying a human body stimulus involves mentally rotating an embodied spatial representation of one's body (motoric embodiment) and projecting it onto the stimulus (spatial embodiment). Interactions between these two processes (spatial and motoric embodiment) may thus reveal cues about the underlying reference frames. The allocentric visual reference frame, and hence the perceived orientation of the body relative to gravity, was modulated using the York Tumbling Room, a fully furnished cubic room with strong directional cues that can be rotated around a participant's roll axis. Sixteen participants were seated upright (relative to gravity) in the Tumbling Room and made judgments about body and hand stimuli that were presented in the frontal plane at orientations of 0°, 90°, 180° (upside down), or 270° relative to them. Body stimuli have an intrinsic visual polarity relative to the environment whereas hands do not. Simultaneously the room was oriented 0°, 90°, 180° (upside down), or 270° relative to gravity resulting in sixteen combinations of orientations. Body stimuli were more accurately identified when room and body stimuli were aligned. However, such congruency did not facilitate identifying hand stimuli. We conclude that static allocentric visual cues can affect embodiment and hence performance in an egocentric mental transformation task. Reaction times to identify either hands or bodies showed no dependence on room orientation.

Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon

We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis recovers, leading to normal propagation velocities of fecal pellets along the colon. This raises the fundamental question: what mechanisms underlie hexamethonium-resistant peristalsis? We investigated whether blockade of the major receptors that underlie excitatory neuromuscular transmission is required for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements was used to make spatiotemporal maps and determine the velocity of peristalsis. Propagation of artificial fecal pellets in the guinea pig distal colon was studied in hexamethonium, atropine, ω-conotoxin (GVIA), ibodutant (MEN-15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In contrast, ω-conotoxin abolished peristalsis in some preparations and reduced the velocity of propagation in all remaining specimens. Peristalsis could still occur in some animals in the presence of hexamethonium + atropine + ibodutant + ω-conotoxin. Peristalsis never occurred in the presence of TTX. The major finding of the current study is the unexpected observation that peristalsis can occur after blockade of the major excitatory neuroneuronal and neuromuscular transmitters. Also, the colon retained an intrinsic polarity in the presence of these antagonists and was only able to expel pellets in an aboral direction. The nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be identified.

Morphology and Luminescence of ZnO Films Grown on a Au(111) Support

Using scanning tunneling microscopy and spectroscopy, we have analyzed the growth of ZnO thin films on a Au(111) support. Because of the 12% lattice mismatch with the metal beneath, ZnO develops a (0001)-oriented coincidence lattice that gives rise to a well-ordered hexagonal Moire pattern with 2.2 nm periodicity. This superstructure disappears at 4 ML film thickness, when wide, atomically flat terraces delimited by straight monatomic steps become detectable in the STM. The long-range order of the films is deduced from sharp hexagonal spot patterns in low-energy electron diffraction. STM-based luminescence and conductance spectroscopy reveals that the ZnO band gap approaches the bulk value in films thicker than 10 ML. Additional photon peaks with sub-band-gap energies indicate the presence of defects in the wurzite lattice. The intrinsic polarity of the ZnO(0001) surface is accounted for by a reduced Zn–O interlayer distance and an adsorption-mediated compensation scheme in thin and thick films, respectively.

Is there a generalized magnitude system in the brain? Behavioral, neuroimaging, and computational evidence

Some 10 years ago, it was proposed that different quantities, including time, space or number, are processed by a common mechanism (Walsh, 2003; Pinel et al., 2004; Cohen Kadosh et al., 2005), henceforth called generalized magnitude system (GMS). This presented an important attempt at theoretically integrating data across various literatures, and became very influential (e.g., Burr et al., 2010; Lourenco and Longo, 2011; Bonato et al., 2012). However, in this paper we will evaluate the concept in a critical way. We first argue that such a mechanism faces conceptual difficulties. Second, we look at empirical findings that were proposed to support a GMS and will offer a different explanation of these findings based on computational modeling and recent empirical observations. Third, we review positive evidence in favor of distinct magnitude mechanisms. We discuss alternatives for a GMS in a final paragraph.

Formative Cell Divisions: Principal Determinants of Plant Morphogenesis

Formative cell divisions utilizing precise rotations of cell division planes generate and spatially place asymmetric daughters to produce different cell layers. Therefore, by shaping tissues and organs, formative cell divisions dictate multicellular morphogenesis. In animal formative cell divisions, the orientation of the mitotic spindle and cell division planes relies on intrinsic and extrinsic cortical polarity cues. Plants lack known key players from animals, and cell division planes are determined prior to the mitotic spindle stage. Therefore, it appears that plants have evolved specialized mechanisms to execute formative cell divisions. Despite their profound influence on plant architecture, molecular players and cellular mechanisms regulating formative divisions in plants are not well understood. This is because formative cell divisions in plants have been difficult to track owing to their submerged positions and imprecise timings of occurrence. However, by identifying a spatiotemporally inducible cell division plane switch system applicable for advanced microscopy techniques, recent studies have begun to uncover molecular modules and mechanisms for formative cell divisions. The identified molecular modules comprise developmentally triggered transcriptional cascades feeding onto microtubule regulators that now allow dissection of the hierarchy of the events at better spatiotemporal resolutions. Here, we survey the current advances in understanding of formative cell divisions in plants in the context of embryogenesis, stem cell functionality and post-embryonic organ formation.

The Levator Veli Palatini Muscle in Artiodactyls—A Comparative Ontogenetic Study

It is accepted in the literature that the levator veli palatini muscle of artiodactyls originates at the ectotympanic bone, a statement based on macroscopic dissection of adult specimens. The study of 34 histological serial sections of fetal heads of 23 species of artiodactyls revealed that this generalization must be modified: in the studied Camelidae, Suidae, Hippopotamidae, Giraffidae, and in some Bovidae (namely Tragelaphus and Antidorcas) the primary attachment of this functionally important muscle is at the tendinous intersection with the tensor veli palatini. Primary ontogenetic attachments are considered as relevant for defining homologies. By outgroup comparison (Felis and Diceros), this structural connection (character state 1) is also found in the Scrotifera—and hence may be considered as plesiomorphic for the Artiodactyla and its subunits. Only in the Tragulidae, Cervidae, Moschidae, and some Bovidae is a secondary attachment at the ectotympanic observed, which is interpreted as apomorphic for these taxa; possibly this character state 2 developed homoplastically several times. Bovidae show a mixed distribution of this character: Tragelaphus, Aepyceros, and Antidorcas show only a connection of the levator with the tensor veli; in Neotragus, Raphicerus, and Sylvicapra there exists an additional insertion at the ectotympanic; only Bos, Cephalophus, Damaliscus, and Ovis have a primary origin at the ectotympanic. It can be demonstrated in late fetal Sus that a secondary insertion of the levator veli at the ectotympanic is established during ontogeny; in a late fetal Ovis a secondary contact with the tensor veli is realized. The interpretation of this character distribution depends not only on an intrinsic polarity (‘Lesrichtung’), but also on the assumed character state of the groundplan of the common ancestor of the Bovidae. The anatomical observations are documented by photographs of relevant histological sections. The character states are mapped on a simplified and synoptic cladogram of extant artiodactyls; their pattern of evolutionary transformation as well as their relevance for the phylogenetic systematics of this mammalian order are discussed.

Rab11 regulates planar polarity and migratory behavior of multiciliated cells in Xenopus embryonic epidermis.

Xenopus embryonic skin is composed of the superficial layer with defined apicobasal polarity and the inner layer lacking the apical domain. Multiciliated cells (MCCs) originate in the inner layer of the epidermal ectoderm and subsequently migrate to the surface. How MCCs acquire the apicobasal polarity and intercalate into the superficial layer during neurulation is largely unknown. As Rab11-dependent vesicle trafficking has been implicated in ciliary membrane assembly and in apical domain formation in epithelial cells, we assessed the involvement of Rab11 in MCC development. Here we report that Rab11 is specifically enriched and becomes apically polarized in skin MCCs. Interference with Rab11 function by overexpression of a dominant negative mutant or injection of a specific morpholino oligonucleotide inhibited MCC intercalation into the superficial layer. Dominant negative Rab11-expressing MCC precursors revealed intrinsic apicobasal polarity, characterized by the apical domain, which is not normally observed in inner layer cells. Despite the presence of the apical domain, the cells with inhibited Rab11 function were randomly oriented relative to the plane of the tissue, thereby demonstrating a defect in planar polarity. These results establish a requirement for Rab11 in MCC development and support a two-step model, in which the initial polarization of MCC precursors is critical for their integration into the superficial cell layer.

Intralineage Directional Notch Signaling Regulates Self-Renewal and Differentiation of Asymmetrically Dividing Radial Glia

Asymmetric division of progenitor/stem cells generates both self-renewing and differentiating progeny and is fundamental to development and regeneration. How this process is regulated in the vertebrate brain remains incompletely understood. Here, we use time-lapse imaging to track radial glia progenitor behavior in the developing zebrafish brain. We find that asymmetric division invariably generates a basal self-renewing daughter and an apical differentiating sibling. Gene expression and genetic mosaic analysis further show that the apical daughter is the source of Notch ligand that is essential to maintain higher Notch activity in the basal daughter. Notably, establishment of this intralineage and directional Notch signaling requires the intrinsic polarity regulator Partitioning defective protein-3 (Par-3), which segregates the fate determinant Mind bomb unequally to the apical daughter, thereby restricting the self-renewal potential to the basal daughter. These findings reveal with single-cell resolution how self-renewal and differentiation become precisely segregated within asymmetrically dividing neural progenitor/stem lineages.

Homo- and Heteronuclear meso,meso-(E)-Ethene-1,2-diyl-Linked Diporphyrins: Preparation, X-ray Crystal Structure, Electronic Absorption and Emission Spectra and Density Functional Theory Calculations

Homo- and heteronuclear meso,meso-(E)-ethene-1,2-diyl-linked diporphyrins have been prepared by the Suzuki coupling of porphyrinylboronates and iodovinylporphyrins. Combinations comprising 5,10,15-triphenylporphyrin (TriPP) on both ends of the ethene-1,2-diyl bridge M(2)10 (M(2) =H(2)/Ni, Ni(2), Ni/Zn, H(4), H(2)Zn, Zn(2)) and 5,15-bis(3,5-di-tert-butylphenyl)porphyrinato-nickel(II) on one end and H(2), Ni, and ZnTriPP on the other (M(2)11), enable the first studies of this class of compounds possessing intrinsic polarity. The compounds were characterized by electronic absorption and steady state emission spectra, (1)H NMR spectra, and for the Ni(2) bis(TriPP) complex Ni(2)10, single crystal X-ray structure determination. The crystal structure shows ruffled distortions of the porphyrin rings, typical of Ni(II) porphyrins, and the (E)-C(2)H(2) bridge makes a dihedral angle of 50° with the mean planes of the macrocycles. The result is a stepped parallel arrangement of the porphyrin rings. The dihedral angles in the solid state reflect the interplay of steric and electronic effects of the bridge on interporphyrin communication. The emission spectra in particular, suggest energy transfer across the bridge is fast in conformations in which the bridge is nearly coplanar with the rings. Comparisons of the fluorescence behaviour of H(4)10 and H(2)Ni10 show strong quenching of the free base fluorescence when the complex is excited at the lower energy component of the Soret band, a feature associated in the literature with more planar conformations. TDDFT calculations on the gas-phase optimized geometry of Ni(2)10 reproduce the features of the experimental electronic absorption spectrum within 0.1 eV.

Colorectal Stents Orient Specimens and Induce Artifacts That Mimic Crohn Disease

Colorectal malignancies may be stented to alleviate obstruction. The stent is a polarized and braided network of metallic wires. Pathology associated with colorectal stents is yet to be described. The authors reviewed 7 cases involving stented colorectal segments from patients lacking clinical suspicion of Crohn disease. In 4 cases, orientation of the specimens and stents matched the corresponding anatomic landmarks. In 3 cases, the specimens lacked helpful anatomic landmarks, and orientation was possible only after correlating with the intrinsic polarity of the stents. Stented areas showed artifacts resembling Crohn disease, including rounded cobblestones, pseudopolyps, and simple fissures, as well as unique artifacts including rhomboid cobblestones, complex fissures, oblique fissures with remarkably straight edges, and conical fragments of tissue that appeared to float. Crohn disease was misdiagnosed in 1 case in which the stent was removed intraoperatively and was never received. Colorectal stents help orient ambiguous specimens and induce patterned injury that can be confused with Crohn disease.

Mechanisms of Stomatal Development

The main route for CO(2) and water vapor exchange between a plant and the environment is through small pores called stomata. The accessibility of stomata and predictable division series that characterize their development provides an excellent system to address fundamental questions in biology. Stomatal cell-state transition and specification are regulated by a suite of transcription factors controlled by positional signaling via peptide ligands and transmembrane receptors. Downstream effectors include several members of the core cell-cycle genes. Environmentally induced signals are integrated into this essential developmental program to modulate stomatal development or function in response to changes in the abiotic environment. In addition, the recent identification of premitotic polarly localized proteins from both Arabidopsis and maize has laid a foundation for the future understanding of intrinsic cell polarity in plants. This review highlights the mechanisms of stomatal development through characterization of genes controlling cell-fate specification, cell polarity, cell division, and cell-cell communication during stomatal development and discusses the genetic framework linking these molecular processes with the correct spacing, density, and differentiation of stomata.

Mob1: defining cell polarity for proper cell division

Mob1 is a component of both the mitotic exit network and Hippo pathway, being required for cytokinesis, control of cell proliferation and apoptosis. Cell division accuracy is crucial in maintaining cell ploidy and genomic stability and relies on the correct establishment of the cell division axis, which is under the control of the cell's environment and its intrinsic polarity. The ciliate Tetrahymena thermophila possesses a permanent anterior-posterior axis, left-right asymmetry and divides symmetrically. These unique features of Tetrahymena prompted us to investigate the role of Tetrahymena Mob1. Unexpectedly, we found that Mob1 accumulated in basal bodies at the posterior pole of the cell, and is the first molecular polarity marker so far described in Tetrahymena. In addition, Mob1 depletion caused the abnormal establishment of the cell division plane, providing clear evidence that Mob1 is important for its definition. Furthermore, cytokinesis was arrested and ciliogenesis delayed in Tetrahymena cells depleted of Mob1. This is the first evidence for an involvement of Mob1 in cilia biology. In conclusion, we show that Mob1 is an important cell polarity marker that is crucial for correct division plane placement, for cytokinesis completion and for normal cilia growth rates.

Vibrated polar disks: spontaneous motion, binary collisions, and collective dynamics

We study the spontaneous motion, binary collisions, and collective dynamics of “polar disks”, i.e. specially designed particles which, when vibrated between two horizontal plates, move coherently along a direction strongly correlated to their intrinsic polarity. The motion of our particles, although nominally three-dimensional and complicated, is well accounted for by a two-dimensional persistent random walk. Their binary collisions are spatiotemporally extended events during which multiple actual collisions happen, yielding a weak average effective alignment. We show that this well-controlled, “dry active matter” system can display collective motion with orientationally-ordered regions of the order of the system size. We provide evidence of strong number density fluctuations in the most ordered regimes observed. These results are discussed in the light of the limitations of our system, notably those due to the inevitable presence of walls.

The Rap1–Rgl–Ral signaling network regulates neuroblast cortical polarity and spindle orientation

A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1-Rgl-Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division.

Comprehensive Profiling of Free and Conjugated Estrogens by Capillary Electrophoresis–Time of Flight/Mass Spectrometry

The biological activity of estrogens is tightly regulated by regioselective phase I/II metabolic transformations that are critical to human health. Current methods for analysis of urinary estrogens are limited by complicated sample pretreatment and/or inadequate specificity for free estrogens and their glucuronide/sulfate conjugates that vary widely in their intrinsic polarity. In this work, direct speciation of intact estrogen conjugates and their regioisomers is demonstrated using capillary electrophoresis-time-of-flight/mass spectrometry (CE-TOF/MS) when using an alkaline buffer system with negative ion mode detection. This method allows for resolution of weakly acidic native estrogens, anionic estrogen conjugates and their positional isomers without significant matrix-induced ion suppression effects in human urine. Identification of unknown estrogen metabolites using CE-TOF/MS is supported by accurate mass together with their characteristic relative migration times, which can be predicted based on two intrinsic physicochemical properties of an ion. CE-TOF/MS offers a promising strategy for comprehensive profiling of estrogens and other classes of steroid conjugates that is needed for deeper insight into the etiology and treatment of chronic disorders associated with impaired estrogen metabolism.

Myosin IIB deficiency in embryonic fibroblasts affects regulators and core members of the par polarity complex

Wild-type (WT) and myosin heavy chain IIB null [MHCIIB (-/-)] embryonic fibroblasts were used as an experimental model to assess the role of the isoform B of myosin II (MII) in the regulation of the cell shape and intrinsic polarity. Genetic ablation of MHCIIB causes a persistent albeit, unstable protrusive activity in embryonic fibroblasts (Lo et al. in Nonmuscle myosin IIB is involved in the guidance of fibroblast migration. Mol Biol Cell 15:982-989, 2004). Here, we show that MHCIIB-deficient fibroblasts are characterized by a sustained guanine nucleotide exchange factor (GEF)-dependent activation of the small GTPase Rac-1 that is responsible for the continual lamellipodium formation. Moreover, we observed a sustained PKC-ζ activation and an increased association of cortactin with the plasma membrane in the MHCIIB (-/-) cells that were also dependent on GEF-mediated Rac-1 activation. Rac-1 activation and its downstream effects were induced in WT fibroblasts by inhibiting MII ATPase and crosslinking activities, suggesting that an altered actin-MII interaction favours Rac-1 activation, regardless of the MII isoform implicated. In addition, we found MIIB isoform-specific effects that were independent of Rac-1 activation. MHCIIA interacts with cortactin whereas MHCIIB does not. By contrast, MHCIIB interacts with Lgl1, a member of the Scribble/Dlg/Lgl polarity complex, whereas MHCIIA does not. MHCIIB (-/-) fibroblasts exhibited deregulated endogenous levels of the Par polarity complex members, Par3 and Par6. Together, the data show that MHCIIB deficiency causes imbalances in signalling pathways that are responsible for cell polarity determination. The results suggest that these pathways are targets of MIIB in the regulation of the cell's shape and polarity.