Placode patterning by the anterior neural border and the Wnt signalling pathway

This project aims to identify the key molecules controlling the formation of the nose and adenohypophysis. These organs develop from adjacent discrete ectodermal thickenings called cranial placodes. These placodes are therefore essential for the development of both sensory and neuro-endocrine systems. We have identified a specific cell population located in the very early central nervous system that is crucial for development of the telencephalon (forming the cortex in human). This special signalling cell population also lies adjacent to the precursors of both nose and adeno-hypophysis. We will explore the role of the signalling cell population (and its known secreted molecules) in controlling the development of these placodes. The cellular and molecular mechanisms leading to the establishment of both the nose and the hypophysis are not yet understood and this study will bring some novel understanding of these processes. It will also participate to the understanding of human genetic abnormalities affecting the development of olfaction, and hormonal dysfunction due to failure in hypophyseal development.

Cranial placodes are discrete ectodermal thickenings that form in specific areas of the vertebrate head. They make crucial contributions to sense organs such as nose and eyes, to hypophysis and to cranial sensory ganglia. They are therefore essential for both head sensory and neuro-endocrine systems. They first appear as discrete regions of thickened ectoderm located near the neural plate. The mechanisms underlying induction of those regions in specific location inside the non-neural ectoderm are poorly understood. To date, it is unclear whether induction itself is already giving identity to the placodal tissue or whether an undefined placodal territory is first induced inside which further refinement in positional information will progressively restrict cell fate to a particular placode.
In zebrafish and in mice, the anterior border of the neuroectoderm (ANB) has been shown to have a key role in instructing the anterior plate to form specific forebrain structures. The identity of the signalling molecules involved in such an organising function begins to be unravelled. One such key signal is a secreted frizzled related Wnt antagonist called Tlc. The ANB signalling centre is located at the border between neural and anterior placodal territory, making it a prime candidate for regulating the identity of the placodes originating from this area (forming the anterior pituitary and nasal pits). This project thus aims to (1) Characterise the role of the ANB in anterior placode formation, (2) Assess the role of the Wnt and Fgf pathways in establishment and patterning of the rostral placodes.