Congress Abstracts - Society for Developmental Biology

Program/Abstract # 202
Serotonin 2B receptor signaling is required for ocular morphogenesis in Xenopus
Ori, Michela; Marras, Giulia; Testa, Giovanna; De Lucchini, Stefania; Nardi, Irma (University of Pisa, Scuola Normale Superiore,
Italy)
Recent work from our laboratory focused on the role of the serotonin 5-HT2B receptor in Xenopus craniofacial and ocular
morphogenesis. 5-HT2B gene is, in fact, expressed in the cranial neural crest cells (NCCs) which contribute to visceral arches and
periocular mesenchyme (POM), a key signaling center required for eye morphogenesis including the choroid fissure closure. We
demonstrated that pharmacologic and genetic alterations in 5-HT2B signaling cause ocular dysgenesis, characterized by small and
dorsalized eyes, disorganized extraocular muscles, a shorter optic nerve and a failure of the choroid fissure closure or coloboma. To
gain insight into the molecular mechanisms of 5-HT2B signaling in eye morphogenesis, we analyzed the gene expression profile of a
number of key genes involved in POM development by in situ hybridization and qPCR in 5-HT2B morphants. POM specific genes
such as Pitx2 and Foxc2, known to be regulated by the retinoic acid (RA), were upregulated and showed altered expression patterns.
Twist, a marker of NCCs derived POM cells, revealed an accumulation of NCCs around the eye and near the ocular fissure suggesting
a possible alteration in NCCs migration during the optic fissure closure and anterior eye segment formation. The Vax2 gene, a marker
of ventral retina did not change its expression domain. Interestingly, the expression of Raldh3, a RA generating enzyme, was
upregulated in 5-HT2B morphants resulting in an expanded expression domain in the ventral retina. On the whole these data support
the notion that 5-HT2B signaling has a key role in the molecular networks of extrinsic factors governing ocular morphogenesis and
suggest a possible interaction between 5-HT and RA signaling during POM development.
Program/Abstract # 203
Jitterbug(jbug)/Filamin is a Hindsight (Hnt) transcriptional target required for axon targeting and tendon cell adaptation to
mechanical stress during Drosophila development.
Olguin, Patricio; Molina, Claudia; López, Estefanía; Sierralta, Jimena (Universidad de Chile, Chile); Oliva, Carlos (KU Leuven,
Belgium)
How neurites grow directionally and find their specific layer in the brain to establish specific synaptic contacts remains poorly
understood. The Drosophila visual system is an excellent model to study this general problem since it shares a similar organization to
vertebrate visual system and its circuits are genetically hardwired and well characterized. This features along with the vast knowledge
of signaling pathways and powerful genetics make it possible to explore molecular mechanisms at the cellular and subcellular level in
the whole organism. Many factors play essential roles during axon growth and layer selection at the growth cone, as chemoatractant
molecules and its receptors, cell adhesion molecules and cytoskeleton regulators. We have found that loss of function (LOF) of
jitterbug(jbug)/Filamin a gene that encodes an acting binding protein that links the cytoskeleton with membrane receptors and
participate of tendon adaptation mechanism to mechanical stress, results in layer targeting defects of photoreceptor (R) axons. These
phenotypes are similar to those associated to the LOF of protein tyrosine phosphatase 69D (PTP69D) which is expressed both in
tendon and R cells. Jbug/Filamin is expressed in photoreceptors under the control of the transcriptional regulator Hindsight and
localizes at the membrane from apical to the axonal terminal. We propose that jbug/Filamin and PTP69D are components of a
mechanotransduction mechanism that works in tendon and photoreceptor cells during its interaction with other tissues during
development. Funded by FONDECYT Nº1120253 and Biomedical Neuroscience Institute, BNI, ICM.
Program/Abstract # 204
Molecular Characterization of Craniofacial Tendons in Zebrafish
Chen, Jessica W.; Tabin, Clifford J. (Harvard Medical School, USA); Galloway, Jenna L. (Center for Regenerative Medicine,
Harvard Stem Cell Institute, Massachusetts General Hospital, USA)
Tendons enable movement by transmitting the force generated by the muscles to the bones. Not only is the integrity and strength of
the attachment important, but the precise location of the connections between muscle, tendon and bone within the body must be
strictly regulated for efficient motion. Due to an essential role of tendons in the mechanics of body movement, cases of tendon injury
and degeneration are significant clinical issues. To date, there are a limited number of zebrafish studies analyzing tendon and ligament
tissues and no reported expression of scleraxis (scx), the most robust mammalian marker of tendons and ligaments. To characterize the
tendon tissue in the zebrafish, we have analyzed the expression of several robust mammalian markers of tendons and ligaments,
including scx, collagen 1a2 and tenomodulin (tnmd), in the craniofacial musculoskeletal connective tissue regions. We find that scx is
a robust marker of tendon progenitors in zebrafish, but is not required for the formation of differentiated craniofacial tendons as
demonstrated by morpholino-mediated knockdown. Co-expression studies with muscle and cartilage markers demonstrate the
presence of xirp2a at myotendinous junctions, and scx and tnmd at sites of muscle attachment to cartilage. Also, we show that the
formation craniofacial tendon populations in zebrafish parallels what has been observed in higher vertebrates. Zebrafish craniofacial
tendon progenitors are neural crest-derived, and can form in the absence of either muscle or cartilage. However, muscle is required for
the maintenance of craniofacial tendon cell fate. We aim to expand our understanding of tendon formation and discover new potential
therapeutic targets in tendon regeneration.
Program/Abstract # 205
Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome
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