Signalling crosstalk at the leading edge controls tissue closure dynamics in the Drosophila embryo.

Raphaël Rousset,Delphine Cérézo,Stéphane Noselli,Nadège Parassol,Fabrice Carballès,Sébastien Schaub

doi:10.1371/journal.pgen.1006640

Raphaël Rousset, Delphine Cérézo + Show 4 more

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https://doi.org/10.1371/journal.pgen.1006640

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Abstract

Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGFβ/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we sought out new JNK target genes through a genomic approach: 25 were identified of which 8 are specifically expressed in the LE, similarly to decapentaplegic or puckered. Quantitative in situ gene profiling of this new set of LE genes reveals complex patterning of the LE along the AP axis, involving a three-way interplay between the JNK pathway, segmentation and HOX genes. Patterning of the LE into discrete domains appears essential for coordination of tissue sealing dynamics. Loss of anterior or posterior HOX gene function leads to strongly delayed and asymmetric DC, due to incorrect zipping in their respective functional domain. Therefore, in addition to significantly increasing the number of JNK target genes identified so far, our results reveal that the LE is a highly heterogeneous morphogenetic organizer, sculpted through crosstalk between JNK, segmental and AP signalling. This fine-tuning regulatory mechanism is essential to coordinate morphogenesis and dynamics of tissue sealing.

Highlights

Epithelial morphogenesis is orchestrated at the cellular level through local shape changes and tension-based dynamics
Dorsal closure of the Drosophila embryo is used as a paradigm to study epithelial sealing and is related to wound healing
To better characterize the leading edge (LE) and its role during dorsal closure (DC), we used microarrays to identify genes expressed under the control of the JNK pathway in the Drosophila embryo (Figs 1A and S1A)

Summary

Introduction

Epithelial morphogenesis is orchestrated at the cellular level through local shape changes and tension-based dynamics. LE polarization leads to a particular organization of the dorsal cell membrane (that in contact with the amnioserosa), which in particular loses adherens junction markers (such as E-Cadherin, ECad) and septate junction markers (such as Discs-large, Dlg) [2, 4, 5]. This redistribution results in the formation of actin-nucleating centers (ANC) from either side of the dorsal membrane that will transmit, along with the adherens junctions, mechanical forces [2, 5, 6]. Non-muscle myosin II is involved in the generation of the four forces thanks to its motor and contractile activities [12]

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