Martinez-Arias Lab

Department of Genetics, University of Cambridge

Karolina Lada

PhD student

kl282@cam.ac.uk
Department of Genetics,
Downing Street, Cambridge
CB2 3EH,England
Telephone: +44 1223 766595
Fax: +44 1223 333992

My work investigates the process of dorsal closure in the Drosophila embryo, a genetically tractable system in which to analyze the molecular and cellular mechanisms that govern epithelial morphogenesis. Dorsal closure, as the name suggests, closes a naturally occurring hole in the fruit fly epidermis. This involves dynamic movements of two epithelial tissues, epidermis and amnioserosa: the contraction of amnioserosa and the dorsalwards migration and fusion of epidermal sheets. Its many parallels with the process of human wound healing have led to its emergence as a model system.

The aim of my PhD is to further elucidate the communication occurring between the amnioserosa and dorsal epidermis. I hope to define the mechanisms by which the diffusible signal Dpp and three other putative members of this pathway, the transcription factors U-shaped (Ush), Hindsight (Hnt), and Pannier (Pnr), regulate expression of the proteins which govern cell shape changes.

In addition, I am assaying the relative instructive inputs delivered by the epidermis and amnioserosa during dorsal closure. To this end, I am utilizing mutants in which the geometry and relative cellular parameters of these tissues are altered (Figure 1). I have shown an inter-dependence between these two tissues, wherein the dynamics of one tissue influence the morphological changes within the other.

We use fixed preparations as well as live imaging microscopy techniques to follow the cell and tissue dynamics in the embryo. High throughput microarray analysis has also been performed to compare loss of function (LOF) and gain of function (GOF) embryos with the wild-type in an attempt to identify transcriptional targets relating to coordination of morphogenetic activity during dorsal closure.

Dorsal views of a wild-type (wt) and string (stg) mutant embryo at the zippering stage of dorsal closure.
Note the drastically different proportions in relative cell geometry of amnioserosa and epidermis when comparing stg to wt. Cell boundaries have been visualized by immunostaining for F-Actin (red) and Scribbled (blue).