PgmNr D81: Hox Transcription Factors and their Cell type-specific Role in Development.

Authors:
I. Lohmann


Institutes
Ruprecht-Karls University, Heidelberg, Heidelberg, DE.


Abstract:

The highly conserved and essential class of transcription factors encoded by the Hox genes specifies cell fates along the anterior-posterior axis of all bilaterian animals. Besides early patterning functions, Hox proteins are also involved in the morphogenesis of various organs and in the homeostasis of cell lineages in adults. This functional diversity is achieved through a high level of transcriptional specificity, since Hox proteins trigger developmental programs with extreme spatial and temporal resolution, even at the level of single cells. One of the processes controlled by Hox proteins is feeding, a crucial behaviour of all animals, which depends on the rhythmic activity of feeding muscles stimulated by specific brain neurons. We identified the Hox transcription factor Deformed (Dfd) to be expressed and functional in specific neurons and muscles, which are essential for feeding in Drosophila. Using genetic, molecular, genomic and behavioural approaches we demonstrate that Dfd is required at subsequent phases in the formation of the feeding unit by directly controlling in a stage-specific manner target genes of motor neuron development, from the initial specification to the establishment of functional synapses. Furthermore, the synchronous regulation of cell adhesion molecules in motoneurons and muscles critical for feeding uncovers Hox proteins as an important factor that might guide the recognition of the interacting synaptic partners. In order to provide vigorous proof for this hypothesis, we use now cell type-specific genomic approaches (INTACT, ChIPseq, RNAseq) to identify the full complement of synaptic molecules in two tissues, the mesoderm and the CNS. By interfering large-scale with synaptic specificity molecules and Hox gene expression, we aim to formulate a Hox-based synaptic specificity code critical for motoneuronal targeting, synaptic wiring and consequently regional motor outputs. Taken together, our multi-scale approach allows us to decipher how the developmentally critical class of Hox transcription factors acquires context-dependent activity and function at the mechanistic level.