Guthrie Lab

Mechanisms of Cranial Motor Nucleus Formation

Although similar neurons frequently group into functional clusters termed nuclei, little is known about why nuclei exist and how they form. We have previously used the chick hindbrain as a platform to unravel the regulation of nucleus formation (nucleogenesis). We have explored the interplay between cell adhesion mediated by cadherins, gap junctions and patterns of spontaneous activity in brainstem motor neurons during this process. Our previous work has shown that perturbing cadherin function disrupts nucleus formation. Using electroporation of the genetically-encoded Calcium indicator GCaMP into chick brainstems, we have recently characterised the patterns of spontaneous activity (SA) within the facial and abducens motor neuron populations. We have shown that manipulating cadherin and gap junction expression patterns within the brainstem disrupts patterns of SA. Further, SA itself regulates nucleus formation.

We have therefore uncovered a novel link between molecular expression and spontaneous activity in orchestrating nucleus formation. We are now moving into the zebrafish system to test the effects of disrupting cell adhesion and activity on nucleogenesis and the development of behaviours such as the optokinetic reflex.