The loss of the kinases SadA and SadB results in early neuronal apoptosis and a reduced number of progenitors

Pratibha Dhumale, Sindhu Menon, Joanna Chiang, Andreas W. Püschel*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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The neurons that form the mammalian neocortex originate from progenitor cells in the ventricular (VZ) and subventricular zone (SVZ). Newborn neurons are multipolar but become bipolar during their migration from the germinal layers to the cortical plate (CP) by forming a leading process and an axon that extends in the intermediate zone (IZ). Once they settle in the CP, neurons assume a highly polarized morphology with a single axon and multiple dendrites. The AMPK-related kinases SadA and SadB are intrinsic factors that are essential for axon formation during neuronal development downstream of Lkb1. The knockout of both genes encoding Sad kinases (Sada and Sadb) results not only in a loss of axons but also a decrease in the size of the cortical plate. The defect in axon formation has been linked to a function of Sad kinases in the regulation of microtubule binding proteins. However, the causes for the reduced size of the cortical plate in the Sada-/-;Sadb-/- knockout remain to be analyzed in detail. Here we show that neuronal cell death is increased and the number of neural progenitors is decreased in the Sada-/-;Sadb-/- CP. The reduced number of progenitors is a non-cell autonomous defect since they do not express Sad kinases. These defects are restricted to the neocortex while the hippocampus remains unaffected.

Original languageEnglish
Article numbere0196698
Issue number4
Number of pages18
Publication statusPublished - 26. Apr 2018
Externally publishedYes


  • Animals
  • Apoptosis
  • Axons/metabolism
  • Brain/metabolism
  • Cells, Cultured
  • Cerebral Cortex/metabolism
  • Embryo, Mammalian/cytology
  • Ki-67 Antigen/metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Neurons/cytology
  • Proliferating Cell Nuclear Antigen/metabolism
  • Protein-Serine-Threonine Kinases/genetics
  • Stem Cells/cytology


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