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Congress Abstracts - Society for Developmental Biology

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Program/Abstract # 507<br />

Slit1a Promotes Axon-Glial Interations to Facilitate Post-Optic Commissure Formation in Zebrafish<br />

Park, Jin Sook (Smith College, USA)<br />

Bilaterally symmetrical organisms must be able to communicate between the two hemispheres of the brain and body. In order to<br />

achieve proper neural connections between the two halves of the central nervous system, axons must navigate across the midline,<br />

<strong>for</strong>ming a commissure. It is known that the Slit-Roundabout signaling system plays a crucial guidance mechanism involved in<br />

commissure <strong>for</strong>mation. Historically, Slit-Robo signaling has been known to function to repel path-finding axons; however, we propose<br />

a new function to this guidance system, in which slit1a may promote axon-astroglial interactions to facilitate post-optic commissure<br />

(POC) <strong>for</strong>mation in the zebrafish <strong>for</strong>ebrain. We show that the cells of the diencephalic glial bridge express slit1a, and global<br />

misexpression of slit1a causes ectopic wandering POC axons. We and others have shown that crossing by POC axons in the you-too<br />

(Gli2DR) mutant is greatly reduced, which is in part due to expanded midline expression of the known repellents slit2 and slit3. We<br />

show here that global misexpression of slit1a in the you-too (Gli2DR) mutant can rescue POC midline crossing. Importantly, POC<br />

axons are always associated with astroglial cells even when either is displaced from their normal positions. This suggests POC axons<br />

and astroglial cells exhibit positive and potentially necessary interactions <strong>for</strong> commissure <strong>for</strong>mation. We hypothesize that Slit1a-Robo<br />

signaling mediates this positive interaction to facilitate POC axons crossing over the prefigured diencephalic glial bridge. We have<br />

demonstrated that loss of Robo1 function by morpholino knockdown in the context of slit1a misexpression is capable of eliminating<br />

the association of wandering POC axons with astroglial cells. These results suggest that slit1a functions distinctly from slit2 or slit3 to<br />

positively promote association of POC axons with astroglial cells in a Robo1-dependent manner during commissure <strong>for</strong>mation in the<br />

zebrafish <strong>for</strong>ebrain. We are currently testing the role of other Roundabout receptors in mediating axon-astroglial interactions during<br />

POC <strong>for</strong>mation.<br />

Program/Abstract # 508<br />

The PCP factor Prickle1b and transcriptional repressor Rest function within facial branchiomotor neurons to regulate their<br />

migration during zebrafish development<br />

Love, Crystal E. (U Chicago, USA); Sirotkin, Howard (Stony Brook, USA); Prince, Victoria (U Chicago, USA)<br />

Facial branchiomotor neurons (FBMNs) migrate from rhombomere (r) 4 to r6 in the hindbrain during development. These neurons fail<br />

to migrate out of r4 in embryos lacking Prickle1b (Pk1b), a component of the planar cell polarity pathway. Localization of Pk1b to the<br />

nucleus of FBMNs is required <strong>for</strong> their proper migration, which suggests a PCP-independent role of Pk1b in this process. Pk1b has<br />

additionally been shown to interact with RE1-silencing transcription factor (Rest), a transcriptional repressor of neuronal maturation<br />

genes, and is required <strong>for</strong> the translocation of Rest to the nucleus in vitro. Rest is depleted from the nucleus of FBMNs in Pk1bdeficient<br />

embryos, suggesting Pk1b is similarly important <strong>for</strong> Rest nuclear localization in these neurons. Consistent with this<br />

hypothesis, we find FBMN migration is disrupted in mutant embryos expressing a nonfunctional Rest protein, and this phenotype is<br />

enhanced in maternal-zygotic mutant embryos. Using Tol2-mediated transgenesis to either derepress or activate Rest targets<br />

specifically within FBMNs, we show that Rest functions within the neurons, rather than in the surrounding neuroepithelium, to<br />

mediate migration. Our data also suggest that FBMNs mature too early when Rest function is disrupted in these neurons, including the<br />

inappropriate expression of Rest target genes. We propose a model in which Pk1b localizes Rest to the nucleus of FBMNs, with Rest<br />

in turn functioning to repress target genes in the FBMNs, and thus maintain their immature, migratory state.<br />

Program/Abstract # 509<br />

Migration of Cajal-Retzius cells in the olfactory region of the developing telencephalon<br />

Frade, Daniela; Varela-Echavarria, Alfredo (UNAM-Queretaro, Mexico)<br />

The mammalian cortex is organized into layers which depend <strong>for</strong> their organization on the glycoprotein Reelin secreted by Cajal-<br />

Retzius cells (CR) located in the outermost layer of the developing telencephalon. CR cells originate mainly in the cortical hem in the<br />

dorsal midline of the telencephalon, but are also known or proposed to be generated from other domains. One of the proposed domains<br />

is the lateral telencephalic region near the boundary between the pallium and subpallium in the ventral pallium (VP) and another one<br />

is located in the rostral region of the rostral cortex. Migration routes of cells in these regions have been little studied. It has been<br />

proposed that CR cells originating from the VP migrate to the dorsal cortex while the cells generated in the rostral region are<br />

positioned in the rostral cortex. We have analyzed the migration of cells in both regions during the stages where CR cells are being<br />

generated. By injecting a fluorescent tracer we observed that labeled cells along the anteroposterior extent of the VP migrate in ventral<br />

direction while cells from the rostral domain migrate caudally along the olfactory region and dorsally to the dorsal cortex. Moreover,<br />

we have observed that about one fourth of the migrating cells express Reelin. These results reveal novel routes of migration of<br />

uncharacterized cells including a Reelin-expressing population in the developing telencephalon.<br />

Program/Abstract # 510<br />

Neogenin/RGMa signaling may regulate polarized migration during neural convergent extension in Danio rerio<br />

Olmo, Valerie; Jayachandran, Pradeepa; Brewster, Rachel (U Maryland-Baltimore County, USA)<br />

The neural tube, the precursor of the CNS, is <strong>for</strong>med by morphogenetic changes that trans<strong>for</strong>m the neuroepithelium into a tubular<br />

structure during neurulation. Though aspects of neurulation vary by species, neural convergent extension (NCE), a very early stage of<br />

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