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Disruption of Tsukushi function result in aberrant neurogenesis in mouse

M. Asrafuzzaman Riyadh1, Ayako Ito¹, Yohei Shinmyo^{1, 2}, Athary Felemban¹, Jun Hatakeyama³, Kenji Shimamura³, Kazunobu Sawamoto⁴ and Kunimasa Ohta¹

(¹Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, ²Department of Biophysical Genetics, Graduate School of Medical Sciences, Kanazawa University , ³Department of Brain Morphogenesis, Kumamoto University, Kumamoto 860-0811 Japan, ⁴Department of Developmental and Regenerative Biology, Nagoya City University, Nagoya 467-860, Japan)

Name of the academic meeting: The 48^th Annual Meeting of the Japanese Society of Developmental Biologist, Tsukuba, Japan (June 2-5, 2015).

Date of presentation: 2015-06-04
Type of presentation: Oral presentation
Poster Number: OP18-4
Discussion Times: 14:20-14:35

The mammalian nervous system arises from coordinated proliferation, differentiation and migration of precursor cells during embryonic and early postnatal development. The subventricular zone (SVZ) is one of two regions where neurogenesis persists in the postnatal brain. Four cell types have been described in the SVZ: 1) ependymal ciliated cells (type E), 2) proliferating type A neuroblasts, 3) slowly proliferating type B cells and 4) actively proliferating type C cells. We found type E cells in SVZ express tsukushi, which is a soluble molecule belongs to the small Leucine-Rich Proteoglycan family, worked as a multiple signaling modulator at the extracellular region by regulating TGF-ß, FGF, Notch, and Wnt signaling cascades. Here we observed aberrant cell proliferation and cell death in tsukushi knockout mice (TSK^-/-). All types of cell (B cell, C cell, A cell) undergo hyper proliferation in TSK^-/- mice. The apoptotic cell number increases three fold in TSK^-/- mice. Double immunostaining confirmed a large population of A cell experiences apoptosis in knockout mice compared with the wild type. Because of these altered cell proliferation and massive apoptosis, the lateral ventricle is expanded in TSK^-/- mice. Using transgenic mice we overexpressed tsukushi in TSK^-/- background and rescued lateral ventricle size. In vitro experiments using neurosphere generated from wild type and TSK^-/- mice supports in vivo findings. Thus using loss of function and gain of function experiment we uncover the role of tsukushi in neurogenesis. We will correlate this phenotype with a common neurological defect.

Thank you very much for supporting my expenses in the conference.