Background: Granule neurons in the hippocampal denate gyrus, more specifically the subgranular zone (SGZ), receive information from the cortex and higher brain regions and participates in learning and memory formation. During development these granule neurons are developed from granule neuron precursors (GNP) that continue to develop substantially directly after the birth and less rapid throughout the rest of a lifetime. Recently, it has been found that the cilia on cells plays a substantial role during development, by concentrating receptors and signal transducers required for growth using the intraflagellar transport machinery (IFT). This article shows how cilia along with Shh signaling are essential for establishment and expansion of GNP's in the postnatal denate gyrus.
Methods:
- cell counting
- in-situ hybridization
- qPCR
Results:
- Cilia null mice (Kif3a) were found to have normal morphology of the Ammon's horn on the hippocampus, however the denate gyruses were much smaller and more disorganized when compared to the wild-type mice. GNP's in the mutant mice were also found to be disorganized and reduced, with only 1/3 as many as the wildtype located in the granual layer instead of the SGZ. To verify the results were in fact from the loss of primary cilia, another mutation was induced to mice that inhibited Ift88, a gene encoding for essential subunits of IFT particles. As shown in previously in Kif3a, Ift88 mice 1/3 of the primary cilia was disfuctional leading to severe decrease in GNP proliferation. Finally it was shown that primary cilia are responsible for properly functioning transcription signal pre and post birth such as Shh, Smo, and SmoM2. Concluding, that primary cilia in the developing and postnatal nervous system are critical in correspondence of Shh, Smo, and SmoM2 signalling in establishing and expanding granule nuclear precursor cells that allow for the proper growth of the hippocampal denate gyrus.
~JI
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