Control of Neuronal Morphology by the Atypical Cadherin Fat3

Deans, Michael R.; Krol, Alexandra; Abraira, Victoria E.; Copley, Catherine O.; Tucker, Andrew F.; Goodrich, Lisa V.

doi:10.1016/j.neuron.2011.06.026

Cited by 97 publications

(135 citation statements)

References 60 publications

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“…Since Fat3 is localized to processes in the IPL (Deans et al, 2011), we hypothesized that Fat3 propagates an overall change in cytoskeletal organization, echoing the effects of other Fat-related proteins on tissue polarity. In support of this idea, phalloidin staining revealed that F-actin was strongly enriched in the IPL of control retinas at postnatal day (P)11 (Fig.…”

Section: Fat3 Is Required For Directed Migration Of Amacrine Cellsmentioning

confidence: 99%

“…1D). Fat3 can be detected in the IPL as soon as it forms (Deans et al, 2011), raising the possibility that this defect in mature amacrine cell morphology reflects an earlier role for Fat3 in the control of the cytoskeleton. Developing amacrine cells undergo rapid and transient changes in cytoskeletal organization that manifest as changes in cell shape.…”

Section: Fat3 Is Required For Directed Migration Of Amacrine Cellsmentioning

confidence: 99%

“…Previously, we showed that the Fat-related protein Fat3 is required for neuronal morphogenesis (Deans et al, 2011). In the retina, amacrine cells project a single dendritic arbor into the inner plexiform layer (IPL), a layer of neuropil that separates cell bodies in the inner nuclear layer (INL) from those in the ganglion cell layer (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Fat3 and Ena/VASP proteins influence the emergence of asymmetric cell morphology in the developing retina

2016

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Neurons exhibit asymmetric morphologies throughout developmentfrom migration to the elaboration of axons and dendrites -that are correctly oriented for the flow of information. For instance, retinal amacrine cells migrate towards the inner plexiform layer (IPL) and then retract their trailing processes, thereby acquiring a unipolar morphology with a single dendritic arbor restricted to the IPL. Here, we provide evidence that the Fat-like cadherin Fat3 acts during multiple stages of amacrine cell development in mice to orient overall changes in cell shape towards the IPL. Using a time-lapse imaging assay, we found that developing amacrine cells are less directed towards the IPL in the absence of Fat3, during both migration and retraction. Consistent with its predicted role as a cell-surface receptor, Fat3 functions cell-autonomously and is able to influence the cytoskeleton directly through its intracellular domain, which can bind and localize Ena/VASP family actin regulators. Indeed, a change in Ena/VASP protein distribution is sufficient to recapitulate the Fat3 mutant amacrine cell phenotype. Thus, Fat-like proteins might control the polarized development of tissues by sculpting the cytoskeleton of individual cells.

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Section: Fat3 Is Required For Directed Migration Of Amacrine Cellsmentioning

confidence: 99%

Section: Fat3 Is Required For Directed Migration Of Amacrine Cellsmentioning

confidence: 99%

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Fat3 and Ena/VASP proteins influence the emergence of asymmetric cell morphology in the developing retina

2016

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“…-/-mutants have altered dendritic morphology (Deans et al, 2011). Fat1 is proposed to control actin dynamics through interactions with Ena/Vasp proteins (Moeller et al, 2004;Tanoue and Takeichi, 2004).…”

Section: And Retinal Cells In Fat3mentioning

confidence: 99%

Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity

et al. 2012

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SUMMARYThe atypical cadherin fat (ft) was originally discovered as a tumor suppressor in Drosophila and later shown to regulate a form of tissue patterning known as planar polarity. In mammals, four ft homologs have been identified (Fat1-4). Recently, we demonstrated that Fat4 plays a role in vertebrate planar polarity. Fat4 has the highest homology to ft, whereas other Fat family members are homologous to the second ft-like gene, ft2. Genetic studies in flies and mice imply significant functional differences between the two groups of Fat cadherins. Here, we demonstrate that Fat family proteins act both synergistically and antagonistically to influence multiple aspects of tissue morphogenesis. We find that Fat1 and Fat4 cooperate during mouse development to control renal tubular elongation, cochlear extension, cranial neural tube formation and patterning of outer hair cells in the cochlea. Similarly, Fat3 and Fat4 synergize to drive vertebral arch fusion at the dorsal midline during caudal vertebra morphogenesis. We provide evidence that these effects depend on conserved interactions with planar polarity signaling components. In flies, the transcriptional co-repressor Atrophin (Atro) physically interacts with Ft and acts as a component of Fat signaling for planar polarity. We find that the mammalian orthologs of atro, Atn1 and Atn2l, modulate Fat4 activity during vertebral arch fusion and renal tubular elongation, respectively. Moreover, Fat4 morphogenetic defects are enhanced by mutations in Vangl2, a 'core' planar cell polarity gene. These studies highlight the wide range and complexity of Fat activities and suggest that a Fat-Atrophin interaction is a conserved element of planar polarity signaling.

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“…fat1 mutant mice die soon after birth and do not form proper glomerular slit junctions in kidneys (Ciani et al, 2003). In the developing retina, interneurons called amacrine cells lose their normal unipolar morphology in fat3 mutant animals, and instead acquire multipolar morphology (Deans et al, 2011). fat3 genetically interacts with the vertebrate fj ortholog fjx1 in regulating this process.…”

Section: 1 Vertebrate Ftmentioning

confidence: 99%