University of Dundee

"Asymmetric division, Notch signaling and neurogenesis in the embryonic spinal cord"

Event Date: 
Thursday, February 21, 2019 - 14:00
Event Location: 
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Host: 
Professor Kate Storey FRSE FMedSci FRSB
Dr Jens Januschke
Event Speaker: 
Dr Xavier Morin
Institution: 
Institut de Biologie de l'École Normale Supérieure, Paris
Event Type: 
Seminar
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Abstract

During vertebrate neurogenesis, progenitor cells undergo asymmetric divisions that maintain a pool of progenitors while producing differentiating neurons. Progenitors display high Notch activity, whereas neurons switch it off. This relies on the asymmetric partitioning of the Notch pathway regulator Mindbomb1 (Mib1). We have shown that the intrinsic asymmetry of centrosomes controls the asymmetric recruitment of Mib1 on spindle poles, priming daughter cells for unequal Notch activity.  Integrity of the neuroepithelium relies on subapical junctions while neurons lose this architecture. Newborn “prospective” neurons delaminate via a sequence of basal nuclear translocation, apical surface constriction and N-cad down-regulation, allowing the loss of adhesion before the cell differentiates. Surprisingly, Notch signaling remains active in prospective neurons during this transition. Upon precocious Notch blockade, nascent neurons disassemble their junctions but fail to reduce their apical surface. This weakens the junctional network and leads to breaches in the ventricular wall. We found that the Dll1 ligand promotes differentiation by reducing Notch signaling through cis-inhibition.  However cis-inhibition is blocked by Mib1 during delamination. This transiently sustains high Notch activity and defers differentiation. A fine-tuned balance between trans-activation and cis-inhibition allows cells to seamlessly delaminate from the ventricular wall as they commit to differentiation.