Transcriptional regulation and cellular strategies in neuroregeneration

L.V. Braccioli

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)


Neurogenesis and gliogenesis are processes that occur during development of the CNS as well as
after insult of the nervous system. These tightly regulated processes take place in specialized niches
during embryogenesis and adulthood to generate functional cells, starting from defined progenitor
cells such as neural stem cells (NSCs). Here we took a multifaceted experimental approach to better
understand NSC biology both in vitro and in vivo. Transcriptional regulation is essential since the
expression of specific genes is the key to control timing and fate of the differentiation process. In this
thesis two NSC transcriptional regulators, Foxp1 and Sox4 are shown to be crucial for control of
neurogenesis and gliogenesis respectively. Mutations in the Foxp1 gene have been associated with
speech defects, autism and other intellectual disabilities (Hamdan et al., 2010; Le Fevre et al., 2013;
Lozano et al., 2015; Palumbo et al., 2013; Sollis et al., 2016), as well as being defined as necessary
for neurogenesis (Bacon et al., 2015). In the work presented in this thesis, we sought to define the
molecular mechanisms mediated by Foxp1 that regulate NSC differentiation. Sox4 has been
described as inhibitor of gliogenesis and myelination in oligodendrocyte precursor cells (Bartesaghi
et al., 2015; Hoser et al., 2007; Potzner et al., 2007). In this context we investigated the role and
molecular mechanisms underlying Sox4-mediated regulation of oligodendrogenesis. The use of
cellular strategies to repair CNS insults has been widely investigated in recent years (Daadi et al.,
2010; Donega et al., 2013; Park et al., 2002; Titomanlio et al., 2011; van Velthoven et al., 2010c).
Here we further evaluate the therapeutic potential of NSCs and MSCs to treat perinatal hypoxicischemic
brain damage (HI). Moreover, the hypothesis of the use of exosomes as a cell-free
alternative as a therapeutic option upon brain insults and HI is here examined.
Original languageEnglish
Awarding Institution
  • University Medical Center (UMC) Utrecht
  • Coffer, Paul, Primary supervisor
  • Heijnen, C.J., Supervisor, External person
  • Nijboer, Cora, Co-supervisor
Award date23 Jun 2017
Print ISBNs978-94-629-5648-3
Publication statusPublished - 23 Jun 2017


  • Neural stem cells
  • Mesenchymal stem cells
  • Transcription
  • Neuroregeneration
  • Stem cell transplantation
  • exosomes


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