The Dlx homeobox genes encode homeodomain transcription factors that are involved in
multiple developmental aspects. In the brain, these genes take part in neuronal migration and
differentiation, more precisely in the migration and differentiation of GABAergic neurons.
Dysfunctions in the GABAergic system can lead to various pathological conditions, where
impaired inhibitory function is one of the main causes of several neuropathies characterized by
neuronal hyperexcitability. The Dlx genes are organized as bi-gene clusters and highly
conserved cis-regulatory elements have been previously characterized to be fundamental for
the regulation of Dlx expression in developing embryos of different vertebrates. The activity of
these regulatory elements and the Dlx genes has been well studied in developmental stages of
mice and zebrafish, but little is known about their activity in the adult brain. The extensive
neurogenesis that takes place in the adult zebrafish brain provides an ideal platform for the
visualization of mechanisms involving dlx genes during adulthood and their possible
involvement in adult neurogenesis. Here we show novel information concerning the expression
of dlx1a, dlx2a, dlx5a and dlx6a in the adult zebrafish brain and provide insight into the identity
of cells that express dlx. We also demonstrate the involvement of dlx genes in brain
regeneration and through lineage tracing, their fate determination in the adult zebrafish brain.
Analyses in the adult zebrafish has revealed that all four dlx paralogs are expressed in the
forebrain and midbrain throughout adulthood and expression is found in almost all areas
presenting continuous proliferation. Most dlx-expressing cells present GABAergic neuronal
identity in the adult forebrain where, in some areas they were identified as the Calbindin
subtype. In some areas of the midbrain, especially within the hypothalamus, many dlxexpressing
cell co-localized with a marker for neural stem cells. However, cells expressing dlx
iii
genes did not co-localize with markers for proliferating cells or for glia. Investigations during
brain regeneration in response to injury in the adult zebrafish brain has revealed that dlx5a
expression decreases shortly after lesion and that the dlx5a/6a bi-gene cluster, more
specifically, dlx5a, is up regulated during the peak of regeneration response proposing a
possible role for dlx during regeneration in adults. Studies of lineage tracing have shown the
progeny of dlx1a/2a-expressing cells in adults are located within small clusters in different areas
of the adult brain where they seem to become mature neurons. Our observations provide a
better understanding about the role of dlx genes during adulthood, further contributing to the
general knowledge of the molecular pathways involved in adult neurogenesis and regeneration
in the zebrafish adult brain.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/40047 |
| Date | 09 January 2020 |
| Creators | Weinschutz Mendes, Hellen |
| Contributors | Ekker, Marc |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
Page generated in 0.002 seconds