Astick, MR; (2012) Fgf regulated cadherin expression in cranial nucleogenesis. Doctoral thesis , UCL (University College London).

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Abstract

A recurrent and evolutionarily ancient mode of neuronal organisation juxtaposes functionally related neurons in to so called neuronal nuclei. Neuronal nuclei are the predominant mode of organisation of motor neurons in the vertebrate hindbrain. The coalescence of nuclei during development, a process known as nucleogenesis, is a crucial step in the construction of neural circuits. However, the signals and molecules which govern nucleogenesis are currently not understood. This study demonstrates that members of the classical (Type II) sub family of cadherin cell-cell adhesion molecules are differentially expressed in cranial motor nuclei of rhombomere (r) 5 and 8 as well as the auditory nuclei of r5 in the chicken hindbrain. The dynamic and differential expression of type II cadherins drives the segregation of motor neurons into spatially distinct nuclei. Normalising the type II cadherin expression profile between two motor nuclei; the dorsal Facial Motor Nucleus and Accessory Abducens Nucleus leads to nucleus desegregation, as indicated by aberrant intermixing of neuronal populations. Refinement of the dynamic cadherin expression in r5 is modulated by Fibroblast Growth Factors (Fgf); specifically Fgf8 which is expressed within r5 itself and mediates its action through the MAPK/ERK signalling pathway. Both up and down regulation of this signalling pathway results in the disruption of nucleogenesis, with associated alterations in cadherin expression. Taken together this suggests a model whereby Fgf signalling modulates the dynamic expression of cadherins, which in turn drives cranial nucleogenesis.

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