Smad-interacting-protein 1 (Sip1) contributes to the establishment of the postnatal neurogenic niche
Elke
Stappers1,
Veronique
Van Den Berghe2,
Ruben
Dries1,
Elise
Peyre3,
Agata
Stryjewska1,
Andrea
Conidi4,
Annick
Francis1,
Wilfred
Van IJcken4,
Nicoletta
Kessaris5,
Magdalena
Götz6,
Laurent
Nguyen3,
Danny
Huylebroeck1, 4 and
Eve
Seuntjens1, 3*
-
1
KU Leuven, Department of Development and Regeneration, Belgium
-
2
King's College, United Kingdom
-
3
University of Liège, GIGA-Neurosciences, Belgium
-
4
Erasmus MC, Netherlands
-
5
UCL, United Kingdom
-
6
Helmholtz Institute, Germany
In the adult mouse brain, neuronal cells are continuously produced in the subventricular zone (SVZ) of the lateral ventricles. These immature neuroblasts migrate tangentially along the rostral migratory stream (RMS) to the olfactory bulb (OB), where they integrate as interneurons in the existing cellular network. Little is known however about the molecular mechanisms that steer the establishment of the postnatal SVZ neurogenic niche. The bulk of the SVZ niche develops from the lateral ganglionic eminence (LGE). Immature neural progenitors that give rise to the olfactory interneurons typically express Pax6. Here, we present Sip1 (Zfhx1b/Zeb2) as a novel factor important for the establishment of the postnatal neurogenic niche.
Recent work in our lab showed that the zinc finger transcription factor Sip1 regulates cortical interneuron specification and migration during embryonic development. We also found that Sip1 is present in the LGE, as well as in the postnatal SVZ niche. These findings suggested that Sip1 might be involved in establishing the postnatal neurogenic niche. We used the Gsh2-Cre mouse line to conditionally delete Sip1 from the LGE during embryonic life. In the mutant, we found a significant raise in Pax6+ cells, but the number of doublecortin+ neurons arriving in the OB through the RMS was reduced. The excessive Pax6+ cells in the mutant migrated through the lateral cortical stream to the ventral forebrain, suggesting they either acquired a different fate or were misrouted. Intriguingly, a portion of these cells were not targeted by Cre, suggesting that Sip1 depletion affects their production in a non-cell-autonomous manner. As a result, the mutant OBs appeared smaller and more rounded at postnatal day 5 (P5), and the different layers were severely disorganized. The Sip1-depleted cells that still managed to reach the OB were disoriented and failed to populate the glomerular layer.
Taken together, our data suggest that Sip1 is necessary to provide the young postnatal SVZ niche with the capacity to generate sufficient numbers of interneuron destined for the OB.
Keywords:
Neurogenesis,
Stem Cells,
differentiation,
knockout mouse,
subventricular zone (SVZ)
Conference:
11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015.
Presentation Type:
Poster presentation
Topic:
Neuroscience
Citation:
Stappers
E,
Van Den Berghe
V,
Dries
R,
Peyre
E,
Stryjewska
A,
Conidi
A,
Francis
A,
Van IJcken
W,
Kessaris
N,
Götz
M,
Nguyen
L,
Huylebroeck
D and
Seuntjens
E
(2015). Smad-interacting-protein 1 (Sip1) contributes to the establishment of the postnatal neurogenic niche.
Front. Neurosci.
Conference Abstract:
11th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2015.89.00008
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Received:
05 May 2015;
Published Online:
05 May 2015.
*
Correspondence:
Dr. Eve Seuntjens, KU Leuven, Department of Development and Regeneration, Leuven, Belgium, eve.seuntjens@kuleuven.be