The epithalamus of the zebrafish contains the dorsal habenulae (Dh), a bilateral pair of nuclei characterized by significant left-right asymmetries in gene expression, anatomy, and connectivity. A screen for mutations that affected habenular laterality identified a nonsense mutation in the sec61a-like 1(sec61al1) gene, which codes for the alpha subunit of the ER translocon, a vital entry point for the maturation and processing of all transmembrane and many secreted proteins. sec61al1 mutants undergo an altered program of neurogenesis, producing excess early-borne neurons of the lateral subnucleus at the expense of the later-borne medial subnucleus. Ultrastructural analysis of the cells lining the 3rd ventricle indicates that periventricular precursor cells, which form an epithelium in wild-type embryos, lose apical-basal polarity in sec61al1 mutants. Furthermore, trafficking of N-cadherin through the Sec61 translocon likely mediates differentiation of dorsal habenula progenitor cells, as morphants depleted for cdh2 (the gene that encodes the N-cadherin protein), also develop symmetric LsDh and cdh2 mutant progenitor cells preferentially contribute to the LsDh class. We conclude that Sec61al1 acts to maintain structural polarity in habenular precursor cells, in turn regulating the timing of asymmetric neurogenesis in the habenular nuclei: in the absence of Sec61al1, progenitor cells of the lateral subnucleus overproliferate and differentiate, ultimately resulting in symmetric habenular nuclei.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-10072012-142025 |
| Date | 09 October 2012 |
| Creators | Doll, Caleb Andrew |
| Contributors | Todd Graham, Lila Solnica-Krezel, Joshua Gamse, David Miller |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-10072012-142025/ |
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