Cell integration of diverse genetic inputs during the morphogenesis of complex organs
JAMES CASTELLI-GAIR HOMBRÍA
Our group studies how two-dimensional epithelial sheets of cells reorganize during development to make specific organs. To address this issue we are following two complementary lines of research: (1) Control of Hox induced morphogenesis and (2) Study of the Drosophila JAK/STAT signalling function during development.
Control of Hox induced morphogenesis:
We have developed two models: The ectodermal endocrine glands (corpora allata and prothoracic glands), and the external respiratory organ of the larva (the posterior spiracles).
The glands allow studying the morphogenesis and evolution of a migratory organ, while the spiracles allow studying how cell shape changes and cell rearrangements contribute to the formation of a tube. Both structures are regulated by complex gene-networks activated by Hox genes.
Dfd, Scr and the endocrine glands: The endocrine control of metamorphosis in insects is mediated by the corpora allata and the prothoracic glands. In diptera these fuse to the corpora cardiaca giving rise to the ring gland.
We found that the corpora allata and the prothoracic gland arise from ectoderm cells homologous to those that in other segments give rise to the trachea. This is one of the most extreme cases of divergent evolution known to date. Both trachea and glands use similar genes for their early development, but soon they start diverging by the activation of specific genes that result in the formation of morphologically and functionally different structures. While the trachea maintain their polarized structure, the glands experience an epithelial to mesenchymal transition. We analyze the genes controlling this transition as well as the signals directing their migration. We have shown that trachea and glands can be converted into each other, suggesting they originated from an ancient repeated metameric structure. This model allows the study of how divergent evolution may have occurred.
Abd-B and the posterior spiracles: We have shown that during spiracle formation, the Hox transcription factor ABD-B activates a unique transcriptional cascade in the eighth abdominal segment that induces the cells to change shape and rearrange their relative positions leading to the invagination of the posterior spiracles. We have found that the targets of this Hox transcriptional cascade include apico-basal cell polarity genes, cadherins and GAP and GEF regulators of the small GTPase Rho, which control the actin cytoskeleton in the spiracle. We are currently analyzing how all these fundamental proteins are co-ordinately modulated to induce the characteristic elongation and rearrangement cell behaviours of the developing spiracles. We have proposed a model to explain how Abd-B recruited during evolution the complex gene network that gives rise to the spiracles.
Study of the Drosophila JAK/STAT signalling function during development:
Work in our laboratory has contributed to demonstrate that the Drosophila JAK/STAT pathway is a streamlined version of the vertebrate pathway. We are using this simpler model to understand how the cytokine ligands are transmitted between cells, how the receptor is activated and how STAT activates its downstream targets. We have shown how the pathway signal transduction proteins are compartmentalized in the epithelial cell to signal efficiently in highly polarised tissues. We are currently studying how STAT target genes are activated specifically in some cells and not in every cell where the pathway is active. This lead us to study in depth several enhancers activated by STAT in specific cell types.