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Foxd3 Regulates Self-Renewal and Multipotency of the Neural Crest Binstitute of Animal Physiology and Genetics, Czech Republic Patricia A

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Foxd3 Regulates Self-Renewal and Multipotency of the Neural Crest Binstitute of Animal Physiology and Genetics, Czech Republic Patricia A CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector 458 Abstracts portion of B1, while expression in posterior, or b-lineage, cells is regions of the mRNA, six sets of primer pairs were designed. Gene activated by the proximal part of B1. A medial portion of B1 contains a expression was first localized in limb buds at stage HH20 in the anterior putative GATA binding site that appears to be required for both anterior region. At HH26 expression was present around the limb bud in the and posterior expression. Interestingly, the intergenic region of the peripheral mesenchyme as well as underlying the AER. At HH29, the cluster, which is important for expression of the Dlx genes in vertebrates, expression became localized to the perichondrium and interdigital does not have a specific activating function in the reporter genes tested. areas; however the cartilage condensations were negative. In the head at Comparison of the B1 element with the cis-regulatory region of a non- HH20, strong MECOM expression was situated in the second pharyngeal homologous transcription factor expressed in the same territory, Ci-fog, arch and weaker expression was found in the first arch and maxillary uncovers short similar sequences arranged in the same order as in CiDll- prominence. Facial expression decreased in intensity and was unde- B. This finding suggests that these co-expressed ectodermal genes share tectable by HH29. Since MECOM was expressed adjacent to the AER (a a similar cis-regulatory organization, even though their coding regions source of FGFs), we tested whether endogenous FGF signaling was are not homologous. necessary to maintain expression. Beads soaked in SU5402 (1 mg/ml) were implanted into distal wing mesenchyme at stage HH20 and HH24. doi:10.1016/j.ydbio.2010.05.182 Down-regulation of MECOM expression was observed 24 h after implantation at both stages. Therefore MECOM may be a novel transcription factor mediating the effects of FGF in limb development. MB is supported by GACR (304/09/0725) and IRP IPAG No. AVOZ Program/Abstract # 143 5045015 and JMR by CIHR grants (MOP-102671). Crosstalk between Jagged–Notch, Edn1, and Bmp signaling pathways patterns the dorsal–ventral axis of the vertebrate face doi:10.1016/j.ydbio.2010.05.184 Gage Crumpa, Elizabeth Zunigaa, Marie Rippena, Courtney Alexanderb, Tom Schillingb aUniversity of Southern California, USA Program/Abstract # 145 bUniversity of California, Irvine, USA The Foxa family and intervertebral disk formation Jennifer Maier, Brian Harfe Development of the face requires the unique shaping of skeletal Dept. of Molec. Gen. & Microbiol., Univ. of Florida, Gainesville, FL, USA elements along the dorsal–ventral (DV) axis. Here we show that Jagged– Notch signaling promotes dorsal identity within the zebrafish face. The intervertebral disk (IVD) is composed of an outer annulus Whereas loss of Jagged–Notch signaling in jag1b mutants or notch2- fibrosus (AF), and an inner, gel-like nucleus pulposus (NP). The NP is morpholino animals results in the dorsal facial skeleton adopting a derived from the notochord in mice. Degeneration of the NP can result in ventral morphology, JAG1 misexpression results in reciprocal ventral to back pain. There are few effective treatments for chronic back pain. dorsal skeletal transformations. Moreover, Jagged–Notch signaling Surgery and painkillers can help to alleviate pain but do not address regulates DV facial patterning by repressing the expression of ventral degeneration of the IVD. Little is known about the mechanisms of IVD genes in dorsal skeletal precursors. Edn1 is thought to be essential for development and degeneration; this information could lead to ventral skeletal patterning, as zebrafish edn1 mutants lack a ventral face. improved treatments. The forkhead box (Fox) genes are expressed in Strikingly, we find that loss of Jagged–Notch signaling partially rescues many tissues and are vital to development and post natal life. Foxa1 and ventral facial development in edn1 mutants, and ectopic Notch signaling Foxa2 genes have been well studied in the endoderm, but not in the is observed in ventral precursors of edn1 mutants. Thus, Edn1 functions notochord. Foxa2 null mice die in utero lacking a notochord. Cre alleles to restrict Notch signaling to dorsal skeletal precursors. What then have been used to ablate Foxa2 in the endoderm. These conditional accounts for normal ventral skeletal patterning in the absence of both alleles have also been used with a Foxa1 null allele to make double Edn1 and Notch signaling? Here we show that Bmp signaling also knockouts. We used these alleles with an inducible ShhERT2cre line to promotes ventral identity in the face, with Jagged–Notch signaling remove Foxa2 in tissues where Sonic hedgehog is expressed in E7.5 regulating dorsal patterning through Bmp inhibition. Gremlin2, a Bmp mouse embryos. Fate-mapping with the Rosa26 reporter allele was antagonist, is a target of Notch signaling in dorsal cells, and Gremlin2 done. Mice null for Foxa1 and lacking Foxa2 in Shh-expressing cells reduction or Bmp4 misexpression leads to similar DV skeletal appear to have a severely deformed NP and a shortened tail. Fate- transformations as those seen in jag1b mutants. Our genetic analysis mapping in these mice suggests defects in the migration of notochord thus reveals how multiple signaling pathways cooperate to define cells to the NP. The AF appears to be normal. Deletion of Foxa1 and Foxa2 discrete identities along the DV facial axis. may affect the expression of other genes required for notochord formation and NP development. Using RNA in situ hybridization, we doi:10.1016/j.ydbio.2010.05.183 examined these notochord/NP markers in the Foxa1; Foxa2 knockout mouse. Study of the role of Foxa family action in IVD development may provide insight into new treatments for disk degeneration. Program/Abstract # 144 doi:10.1016/j.ydbio.2010.05.185 Cloning and expression of chicken MECOM/EVI-1 during embryonic limb and face development Marcela Buchtovaa,b, Simona Balkovaa, Joy M. Richmanc aUniversity of Veterinary and Pharmaceutical Sciences Brno, Program/Abstract # 146 Czech Republic Foxd3 regulates self-renewal and multipotency of the neural crest bInstitute of Animal Physiology and Genetics, Czech Republic Patricia A. Laboskya,b, Nathan A. Mundellb cUniversity of British Columbia, Vancouver, Canada aDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232-0494, USA Ecotropical viral integration site 1 (EVI-1/MECOM) is a zinc finger bDepartment of Pharmacology, Vanderbilt University School of Medicine, transcription factor essential for vascularization and cell proliferation Nashville, TN, 37232-0494, USA during embryonic development. Mouse and human MECOM sequences were blasted into ENSEMBL database and homologous chicken gene Neural crest consists of multipotent stem cells and fate-restricted reference sequence is XM_422804. In order to create probes to different progenitors. Mechanisms controlling neural crest self-renewal and Abstracts 459 multipotency and the molecular distinctions between multipotent Slug/Snail2, Snail1 or Twist led to reduction in Xbra and Antipodean/ versus restricted progenitors are poorly understood. Using genetic VegT RNA levels; ii) loss of Xbra/Antipodean led to a decrease in and in vitro manipulations we demonstrate here that the stem cell Slug/Snail2-Snail1-Twist RNA levels, and iii) injection of Slug/Snail2 protein Foxd3 is required for self-renewal and maintenance of or Twist RNAs rescued the Xbra/Antipodean morpholino phenotype. multipotency in the neural crest. In the overlapping cardiac and These data clearly indicate that, in vivo, neural crest formation is vagal neural crest domains, Foxd3 mutant neural crest generated totally dependent upon signals from mesoderm, and that the myofibroblast progenitors located ectopically in the distal aorta, and mesoderm specification network is highly interconnected. This work neural derivatives were lost, suggesting alterations in cell fate. is supported by NIH grant 84133. Individual neural crest cells were no longer multipotent and did not self-renew normally, failed to maintain stem cell marker expression, doi:10.1016/j.ydbio.2010.05.188 and myofibroblast-restricted progenitors were over-represented in mutant cultures. Together, our data show that Foxd3 maintains stem cells of the neural crest by repressing differentiation into non-neural Program/Abstract # 149 lineages, drawing important parallels between neural crest and other Towards understanding the prdm1a gene regulatory network in stem cell populations that depend on conserved regulatory mechan- Danio rerio isms for control of these defining stem cell characteristics. Kristi LaMonica, Kristin Artinger Department of Craniofacial Biology, School of Dental Medicine, UC doi:10.1016/j.ydbio.2010.05.186 Denver, Anschutz Medical Campus, Aurora, CO 80045, USA Proper migration of cranial neural crest cells (cncc) into the Program/Abstract # 147 pharyngeal arches and subsequent interaction with the surrounding Loss of Snail1 leads to loss of mesoderm and neural crest in environment is necessary for formation of the adult craniofacial Xenopus skeleton. prdm1a is a zinc-finger containing transcription factor that Jianli Shi, Courtney Severson, Michael W. Klymkowsky has previously been shown to be expressed in the cncc and posterior MCD Biology UC Boulder, Boulder, CO 80309, USA pharyngeal arches in Danio rerio.Lossofprdm1a
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