PgmNr Z6239: Integration of multiple signaling pathways in habenular development.

Authors:
S. Roberson 1,2 ; M. E. Halpern 1,2


Institutes
1) Carnegie Institution for Science, Baltimore, MD; 2) Johns Hopkins University, Baltimore, MD.


Abstract:

The habenulae are paired nuclei of the epithalamus, which have been implicated in a number of behaviors, such as sleep, fear/anxiety and reward, as well as in neurological diseases such as bipolar and major depressive disorder. Despite the importance of the habenulae, relatively little is known about their development. Wnt and Fgf signaling pathways have been implicated in the formation of the dorsal habenular (dHb) nuclei, but their interaction during dHb development has not been explored. Both pathways are necessary for the generation of habenular progenitors, which are recognized by their expression of the homeodomain transcription factor dbx1b (Dean et al., 2014, Vue et al., 2007). This progenitor population is dramatically reduced in fgf8 and wntless mutants. Using lineage tracing, we confirmed that dbx1b-expressing progenitors contribute to the entire dHb of larval and adult zebrafish. The dbx1b-expressing progenitors were also found to persist past 12 days post fertilization.  It was previously suggested that the chemokine receptor Cxcr4b was also produced in habenular progenitors or early habenular neurons. Our data indicate that cxcr4b is not transcribed in habenular progenitors; rather, cxcr4b expression increases as dbx1b expression decreases, supporting the hypothesis that cxcr4b demarcates newly born habenular neurons. Wnt and Fgf signaling both regulate the spatial domain of expression of chemokine pathway components in the dorsal diencephalon, with Wnt acting upstream of Fgf8.  We will present new findings on both the function of the chemokine signaling pathway in habenular development and the role of Wnt and Fgf signaling in this pathway.



ZFIN Genetics Index
1. wls
2. fgf8a
3. dbx1b
4. cxcr4b