Leading edge‐secreted Dpp cooperates with ACK‐dependent signaling from the amnioserosa to regulate myosin levels during dorsal closure

Zahedi, Baharak; Shen, Weiping; Xu, Xingshun; Chen, Xi; Mahey, Meena; Harden, Nicholas

doi:10.1002/dvdy.21722

Cited by 20 publications

(33 citation statements)

References 47 publications

(79 reference statements)

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“…Loss-of-function alleles for both Drosophila Ack and PR2 have been described previously [29]. Ack 86 is a protein null allele that was generated by imprecise excision of the P element insertion KG00869 [29], [30].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Ack 86 is a protein null allele that was generated by imprecise excision of the P element insertion KG00869 [29], [30]. Homozygous Ack 86 flies appear visually normal, although females homozygous for Ack 86 are fertile while homozygous males are sterile [29]. Genes that are involved in programmed cell death regulation and execution are implicated in Drosophila male fertility because apoptosis-like events are required for sperm cell individualization [31].…”

Section: Resultsmentioning

confidence: 99%

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Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

et al. 2012

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Activated Cdc42 kinases (Acks) are evolutionarily conserved non-receptor tyrosine kinases. Activating somatic mutations and increased ACK1 protein levels have been found in many types of human cancers and correlate with a poor prognosis. ACK1 is activated by epidermal growth factor (EGF) receptor signaling and functions to regulate EGF receptor turnover. ACK1 has additionally been found to propagate downstream signals through the phosphorylation of cancer relevant substrates. Using Drosophila as a model organism, we have determined that Drosophila Ack possesses potent anti-apoptotic activity that is dependent on Ack kinase activity and is further activated by EGF receptor/Ras signaling. Ack anti-apoptotic signaling does not function through enhancement of EGF stimulated MAP kinase signaling, suggesting that it must function through phosphorylation of some unknown effector. We isolated several putative Drosophila Ack interacting proteins, many being orthologs of previously identified human ACK1 interacting proteins. Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. Drk is the Drosophila homolog of GRB2, which is required to couple ACK1 binding to receptor tyrosine kinases. Drk knockdown blocks Ack survival activity, suggesting that Ack localization is important for its pro-survival activity. Yorkie is a transcriptional co-activator that is downstream of the Salvador-Hippo-Warts pathway and promotes transcription of proliferative and anti-apoptotic genes. We find that yorkie and Ack synergistically interact to produce tissue overgrowth and that yorkie loss of function interferes with Ack anti-apoptotic signaling. Our results demonstrate how increased Ack signaling could contribute to cancer when coupled to proliferative signals.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

et al. 2012

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“…Dynamic actin-rich filopodia are projected from the leading edge (LE) and at the final stage of closure they interdigitate with filopodia from the opposing epidermal front, actively zipping the epidermal sheets together (Jacinto et al, 2000; Hutson et al, 2003; Peralta et al, 2007; Millard and Martin, 2008). Thus DC results from the joint contribution of AS and epidermis-specific forces, spanning multi-cellular distances, and several studies have suggested mechanical and chemical interactions between the two tissues (Kiehart et al, 2000; Reed et al, 2001; Stronach and Perrimon, 2002; Scuderi and Letsou, 2005; Fernandez et al, 2007; Gorfinkiel and Martínez Arias, 2007; Wada et al, 2007; Zahedi et al, 2008; Gorfinkiel et al, 2009; Solon et al, 2009). However, the control and coordination of these interactions has not been explored.…”

Section: Introductionmentioning

confidence: 99%

“…Dpp, a ligand of the TGF-β superfamily, is then secreted from the DME to promote autocrine and paracrine signaling with essential roles in morphogenesis of both epidermis and amnioserosa (Hou et al, 1997; Riesgo-Escovar and Hafen, 1997; Sluss and Davis, 1997; Su et al, 1998; Ricos et al, 1999; Arquier et al, 2001; Chen et al, 2002; Fernandez et al, 2007; Wada et al, 2007). The latter is particularly of interest since it represents a form of communication between the tissues: a chemical message (Dpp) is released from the epidermis and elicits contraction of the adjacent amnioserosa, in a parallel manner to paracrine TGF-β-induced wound bed contraction in mammals (Martin et al, 1993; Fernandez et al, 2007; Zahedi et al, 2008). Dpp has been shown to affect different cellular activities but little is known about its effectors.…”

Section: Introductionmentioning

confidence: 99%

Interactions between the amnioserosa and the epidermis revealed by the function of the u-shaped gene

2012

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SummaryDorsal closure (DC) is an essential step during Drosophila development whereby a hole is sealed in the dorsal epidermis and serves as a model for cell sheet morphogenesis and wound healing. It involves the orchestrated interplay of transcriptional networks and dynamic regulation of cell machinery to bring about shape changes, mechanical forces, and emergent properties. Here we provide insight into the regulation of dorsal closure by describing novel autonomous and non-autonomous roles for U-shaped (Ush) in the amnioserosa, the epidermis, and in mediation of communication between the tissues. We identified Ush by gene expression microarray analysis of Dpp signaling targets and show that Ush mediates some DC functions of Dpp. By selectively restoring Ush function in either the AS or the epidermis in ush mutants, we show that the AS makes a greater (Ush-dependent) contribution to closure than the epidermis. A signal from the AS induces epidermal cell elongation and JNK activation in the DME, while cable formation requires Ush on both sides of the leading edge, i.e. in both the AS and epidermis. Our study demonstrates that the amnioserosa and epidermis communicate at several steps during the process: sometimes the epidermis instructs the amnioserosa, other times the AS instructs the epidermis, and still other times they appear to collaborate.

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Sec61α is required for dorsal closure during Drosophila embryogenesis through its regulation of Dpp signaling

Wang¹,

Ward²

2010

Developmental Dynamics

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During dorsal closure in Drosophila, signaling events in the dorsalmost row of epidermal cells (DME cells) direct the migration of lateral epidermal sheets towards the dorsal midline where they fuse to enclose the embryo. A Jun amino-terminal kinase (JNK) cascade in the DME cells induces the expression of Decapentaplegic (Dpp). Dpp signaling then regulates the cytoskeleton in the DME cells and amnioserosa to affect the cell shape changes necessary to complete dorsal closure. We identified a mutation in Sec61a that specifically perturbs dorsal closure. Sec61a encodes the main subunit of the translocon complex for co-translational import of proteins into the ER. JNK signaling is normal in Sec61a mutant embryos, but Dpp signaling is attenuated and the DME cells fail to maintain an actinomyosin cable as epithelial migration fails. Consistent with this model, dorsal closure is rescued in Sec61a mutant embryos by an activated form of the Dpp receptor Thick veins. Developmental Dynamics 239:784-797,

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Leading edge‐secreted Dpp cooperates with ACK‐dependent signaling from the amnioserosa to regulate myosin levels during dorsal closure

Cited by 20 publications

References 47 publications

Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

Interactions between the amnioserosa and the epidermis revealed by the function of the u-shaped gene

Sec61α is required for dorsal closure during Drosophila embryogenesis through its regulation of Dpp signaling

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