Congress Abstracts - Society for Developmental Biology

growth factors used to keep them alive and dividing is not known. We focus in determining the role of Fgf2 in this change in plasticity
in culture. We found that even at the lowest dose required for survival and proliferation, change in the differentiation potential is
noted. This effect was accelerated at higher doses. Interestingly, under inhibition of the PI3K signaling pathway, Fgf2 promoted
neuronal differentiation of cultured NPCs, whereas astrocytes were obtained if, instead, MAPK pathway is blocked. Therefore, a
single growth factor may activate conflicting signals causing the loss of NPCs original properties and unpredictable differentiation
outcome. Supported by CONACyT 50956 and 131031
Program/Abstract # 476
Sensory diversity in the olfactory system: left-right neuronal asymmetry
Chuang, Chiou-Fen Chuang (Cincinnati Children's Research Foundation, USA)
Left-right asymmetry is an important aspect of normal brain development and function in organisms from worms to humans.
Reduced and reversed brain asymmetry has been linked to a variety of neurodevelopmental disorders including autism and dyslexia.
However, the mechanisms underlying lateralization of the developing nervous system are not completely understood. One way to
generate brain asymmetry is to specify different fates and functions of individual cell types across the left-right axis. The C. elegans
left and right AWC olfactory neurons differ in their expression of chemosensory receptor genes and in their functions. We previously
showed that cell-cell communication between AWC neurons and non-AWC neurons through a transient, embryonic gap junction
network (which consist of both AWCs and ~34 other neurons) establishes stochastic left-right AWC asymmetry, which is maintained
throughout the life of an animal. I will present our recent findings that provide additional insights into the molecular mechanisms that
specify AWC asymmetry. As mutations in the human homologs of the genes we study are associated with a variety of developmental
disorders, understanding normal functions of these genes in mechanistic detail will inform novel therapeutic strategies.
Program/Abstract # 477
Mechanism of myelin basic protein mRNA localization
Meireles, Ana; Talbot, William (Stanford, USA)
Myelin is a specialized sheath that allows axons in the vertebrate nervous system to rapidly conduct action potentials. Myelin is
disrupted in Multiple Sclerosis and other debilitating diseases, underscoring the importance of myelin in human health. In the brain
and spinal cord, oligodendrocytes extend processes to multiple axons and form myelin around many axonal segments. In addition to
specialized lipids and myelin proteins, oligodendrocyte myelin also contains mRNAs encoding Myelin Basic Protein (MBP) and a few
other proteins. Although it is striking that these mRNAs are specifically localized in myelin, the mechanism and function of the RNA
localization process are not well understood. We are working to test the hypothesis that mbp mRNA is localized to myelin to prevent
MBP protein from accumulating in the oligodendrocyte cell body, where it might disrupt other cellular compartments by triggering
ectopic membrane compaction. As a first step, we have developed a transgenic assay system to define sequences in the mbp mRNA
that are sufficient to localize a heterologous RNA to myelin in oligodendroyctes in vivo. In preliminary studies, we have examined
localization of 11 chimeric RNAs containing the coding sequence of mCherry and different segments of the mbp RNA. These
experiments have defined a sequence of approximately 400 nt from the mbp 3’ UTR that is sufficient for myelin localization. We are
working to analyze TALEN-induced deletions in the mbp 3’UTR to identify essential localization sequences, and also to examine the
effects of expression of mislocalized mbp mRNAs in vivo.
Program/Abstract # 478
Chemical and genetic screening for factors that regulate myelination in zebrafish
Petersen, Sarah C.; Monk, Kelly R. (Washington U, USA)
Myelin is a multilayered membrane that ensheathes axons and is crucial for neuronal function and survival. Although myelin is an
essential component of vertebrate nervous systems, the mechanisms governing its development are not completely understood. A
forward mutagenesis screen designed to reveal factors necessary for myelination uncovered gpr126. In these mutants, Schwann cells
migrate and encompass peripheral axons but fail to wrap the axon (Monk et al. 2009, Monk et al., 2011). gpr126 encodes an adhesion
G protein-coupled receptor (ad-GPCR) which are purported to have dual roles in cell-cell or cell-matrix interactions and signal
transduction. However, most ad-GPCRs, including Gpr126, are undercharacterized and orphaned. We are dissecting the role of
Gpr126 in peripheral myelination with genetic and chemical screens utilizing a hypomorphic, point-mutant allele of gpr126 that has
reduced peripheral myelin in zebrafish larvae. With the aid of a transgenic fluorescent myelin marker, we are screening for mutations
and small molecules that enhance or suppress the hypomorphic gpr126 phenotype. Our pilot genetic screen has revealed two potential
mutants that interact with gpr126: one, a candidate suppressor mutation that restores myelination, and two, a candidate enhancer
mutation that results in hypomyelination in gpr126 heterozygotes. Additionally, we have found multiple suppressor chemicals that
promote myelination in gpr126 hypomorphs. These represent potential exogenous ligands and could serve as therapeutic compounds
for peripheral myelinopathies. Current studies are focused on identifying the genetic lesions that interact with gpr126 and
characterizing the small molecules that promote Gpr126 function.
Program/Abstract # 479
RPE specification is mediated by surface ectoderm-derived BMP and Wnt signalling in the chick
Steinfeld, Jörg, (Technische Universität Darmstadt, Germany); Steinfeld, Ichie (Nara Women's University, Japan); Coronato, Nicola;
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