Molecular mechanisms of ectodermal specification

Much research has been done into how ectodermally-derived cells and tissues are specified during embryonic development, less however is known as to how, once specified, differentiation into specific cell types occurs. An important gap in our knowledge is in understanding the forces that drive this differentiation and subsequent morphogenesis of cells. I have been interested in the molecular cues that partition the ectoderm to become neural (Muñoz-Sanjuán et al, 2002; Bell et al, 2003) and how different territories are regionalized (Bates et al, 2013). Once specified, a key question that follows is how cells within the neuralised territories are organised to perform the distinctive behaviours that define their first steps in differentiation to distinct fates. These early differentiation behaviours include epithelial thickening and folding, delamination and migration, and are essential to the development of the peripheral and central nervous system.

Ectoderm is specified by a combination of inductive and inhibitory cues. Coco, a TGFβ and Wnt inhibitor, is expressed maternally in the animal pole of the egg. In order to understand whether Coco functions as a neural inducer, we have used both the host transfer technique and morpholinos to knockdown its function. We have demonstrated that Coco is required to prevent mesendodermal signals from acting more animally. Knockdown of Coco affects ectodermal specification (Bates et al, 2013). These embryos have an increase in endoderm formation due to the increase in Xnr and Activin signaling more animally. In order to gain further insights into how Coco functions, we have performed a microarray screen to identify downstream targets. We are currently analyzing these in more detail.

Placodes are transient thickenings of the cranial ectoderm that contribute to the sensory apparatus of the head. The developing placodes derive from a common preplacodal region that forms adjacent to the neural plate and expresses an array of transcription factors. Much progress has been made in understanding the specification of cell types during placode formation, rather less is known about the regulation of the factors that direct the morphogenesis of the placodes and their particular derivatives. We are currently investigating these processes.