View Program - 63rd Annual Drosophila Research Conference

Epithelial sheets of cells are a fundamental building block of animal tissue. To build functional, proportional organs, epithelia must coordinate their growth with the growth of other epithelial and non-epithelial tissues. How this synchronized growth occurs is a key question in developmental biology. To understand coordinated epithelial growth, we turned to the wing imaginal disc, a larval organ that develops into the adult wing and thorax. The wing disc consists of two layers of simple epithelia that are connected at their edges (similar to a pita pocket). These two layers have very different morphologies – the disc proper (DP) is composed of many tightly-packed columnar cells, while the peripodial epithelium (PE) is made up of relatively few cells that are very flat and broad – but despite their differences, the two layers grow at the same speed throughout larval development. We wanted to know what regulates growth of the PE, and how it keeps pace with the DP, in order to better understand how epithelial proportionality is maintained during development.
We found that even though the two layers grow at the same speed, they use very different pathways to do so. Growth of the DP absolutely requires the secreted morphogens Hedgehog and Dpp, but we found that most PE growth can occur without these signals. In contrast, several components of the mechanosensitive Hippo pathway, including Yorkie (Yki) and multiple transcriptional cofactors, are critical for growth of the PE. Yki is required for PE survival and proliferation, as it is in many tissues, but it also mediates the dramatic cell shape changes that are unique to this layer of the disc.
Yki activity can be upregulated by mechanical stretching forces, and so could directly link growth of the PE to growth of the DP. We speculate that DP growth stretches the PE, which increases PE Yki activity. Increased Yki activity, in turn, promotes growth of the PE, so that the two layers grow at the same speed. In this case, use of two very different growth paradigms – one based on morphogen gradients, and one based on mechanical force – seems to be the key to synchronized epithelial growth.

The flipside of tissue growth: how the two layers of the wing imaginal disc keep pace with each other