The roles of the cadherins Fat and Dachsous in planar polarity specification in <i>Drosophila</i>

Thomas, Chloe; Strutt, David

doi:10.1002/dvdy.22736

Cited by 99 publications

(87 citation statements)

References 114 publications

(219 reference statements)

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“…ft is expressed in a relatively uniform pattern throughout the eye disc, whereas ds is expressed in a gradient with highest levels at the poles. Mutations in the Fat/Ds system cause strong PCP defects throughout the entire disc (Yang et al, 2002;Rawls et al, 2002;Simon, 2004;Brittle et al, 2012;Thomas and Strutt, 2012;Sharma and McNeill, 2013;Ayukawa et al, 2014). By contrast, the eyes of homozygous loss-of-function fj mutant alleles are characterized by relatively weak PCP defects (Zeidler et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Extramacrochaetae functions in dorsal-ventral patterning ofDrosophilaimaginal discs

Spratford

Kumar

2015

Development

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One of the seminal events in the history of a tissue is the establishment of the anterior-posterior, dorsal-ventral (D/V) and proximal-distal axes. Axis formation is important for the regional specification of a tissue and allows cells along the different axes to obtain directional and positional information. Within the Drosophila retina, D/V axis formation is essential to ensure that each unit eye first adopts the proper chiral form and then rotates precisely 90°in the correct direction. These two steps are important because the photoreceptor array must be correctly aligned with the neurons of the optic lobe. Defects in chirality and/or ommatidial rotation will lead to disorganization of the photoreceptor array, misalignment of retinal and optic lobe neurons, and loss of visual acuity. Loss of the helixloop-helix protein Extramacrochaetae (Emc) leads to defects in both ommatidial chirality and rotation. Here, we describe a new role for emc in eye development in patterning the D/V axis. We show that the juxtaposition of dorsal and ventral fated tissue in the eye leads to an enrichment of emc expression at the D/V midline. emc expression at the midline can be eliminated when D/V patterning is disrupted and can be induced in situations in which ectopic boundaries are artificially generated. We also show that emc functions downstream of Notch signaling to maintain the expression of four-jointed along the midline.

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Section: Introductionmentioning

confidence: 99%

Extramacrochaetae functions in dorsal-ventral patterning ofDrosophilaimaginal discs

Spratford

Kumar

2015

Development

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“…The Drosophila fat gene encodes an atypical cadherin that functions as a receptor for signal transduction pathways that regulate growth (Hippo signaling) and planar cell polarity (PCP) (reviewed by Thomas and Strutt, 2012;Staley and Irvine, 2012). Fat is regulated by two proteins expressed in gradients: Dachsous (Ds) and Four-jointed (Fj).…”

Section: Introductionmentioning

confidence: 99%

“…Fat is regulated by two proteins expressed in gradients: Dachsous (Ds) and Four-jointed (Fj). Ds encodes an atypical cadherin that can function as a ligand for Fat (reviewed by Thomas and Strutt, 2012;Staley and Irvine, 2012). Fj is a Golgi-localized kinase that phosphorylates cadherin domains of Fat and Ds to modulate binding between them (Ishikawa et al, 2008;Brittle et al, 2010;Simon et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Fj is a Golgi-localized kinase that phosphorylates cadherin domains of Fat and Ds to modulate binding between them (Ishikawa et al, 2008;Brittle et al, 2010;Simon et al, 2010). Rather than responding solely to the level of Ds and Fj, Fat is also regulated by the slope and vector of their expression gradients, with the slope influencing Hippo signaling and the vector influencing PCP (Rogulja et al, 2008;Willecke et al, 2008;Thomas and Strutt, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Signal transduction by the Fat cytoplasmic domain

et al. 2013

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SUMMARYThe large atypical cadherin Fat is a receptor for both Hippo and planar cell polarity (PCP) pathways. Here we investigate the molecular basis for signal transduction downstream of Fat by creating targeted alterations within a genomic construct that contains the entire fat locus, and by monitoring and manipulating the membrane localization of the Fat pathway component Dachs. We establish that the human Fat homolog FAT4 lacks the ability to transduce Hippo signaling in Drosophila, but can transduce Drosophila PCP signaling. Targeted deletion of conserved motifs identifies a four amino acid C-terminal motif that is essential for aspects of Fat-mediated PCP, and other internal motifs that contribute to Fat-Hippo signaling. Fat-Hippo signaling requires the Drosophila Casein kinase 1ε encoded by discs overgrown (Dco), and we characterize candidate Dco phosphorylation sites in the Fat intracellular domain (ICD), the mutation of which impairs Fat-Hippo signaling. Through characterization of Dachs localization and directed membrane targeting of Dachs, we show that localization of Dachs influences both the Hippo and PCP pathways. Our results identify a conservation of Fat-PCP signaling mechanisms, establish distinct functions for different regions of the Fat ICD, support the correlation of Fat ICD phosphorylation with Fat-Hippo signaling, and confirm the importance of Dachs membrane localization to downstream signaling pathways.

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“…The current model is based on the heterophilic interaction between these two single-pass transmembrane proteins. This interaction generates a signaling cascade mediated by the Ft intracellular domain, which results in cytoskeletal reorganization and the modulation of the Hippo pathway [2,3].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional analysis of the dachsous gene uncovers novel isoforms expressed during development in Drosophila

et al. 2015

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a b s t r a c tThe Drosophila cadherin-related protein Dachsous (Ds) plays a prominent role in planar cell polarity (PCP) and growth. The regulation of these two processes is based on the interaction between Ds and Fat proteins, generating an intracellular response required for tissue polarization and modulation of Hippo pathway activity. Here we have performed a comprehensive molecular study of the ds gene during larval development that has shown an unexpected complexity in its transcriptional regulation and revealed the expression of hitherto unsuspected transcripts. Also, knockdown of several isoforms provides new evidence on the importance of the cytoplasmic domain in the mechanism of action of Ds during development.

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The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila

Cited by 99 publications

References 114 publications

Extramacrochaetae functions in dorsal-ventral patterning ofDrosophilaimaginal discs

Extramacrochaetae functions in dorsal-ventral patterning ofDrosophilaimaginal discs

Signal transduction by the Fat cytoplasmic domain

Transcriptional analysis of the dachsous gene uncovers novel isoforms expressed during development in Drosophila

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