Congress Abstracts - Society for Developmental Biology

Program/Abstract # 353
The Facial Neural Crest Controls Fore- and Midbrain patterning by Regulating Foxg1 Expression Through Smad1
Creuzet, Sophie; Aguiar, Diego (CNRS- Institute of Neurobiology, France)
In Vertebrate embryo, the Facial Neural Crest (FNC) provides the forebrain with a skeletal, meningeal protection and a functional
vasculature. It also controls the activity of brain organizers and stimulates cerebrum growth, but the repertoire of the molecules
produced by the FNC to mediate its effect is unknown. To understand how FNC conveys its trophic effect, we have studied the role of
Smad1, expressed in premigratory FNC cells—an intracellular transducer to which multiple signaling pathways converge — in the
regulation of Foxg1. Foxg1 is a transcription factor essential for telencephalic specification, the mutation of which leads to
microcephaly and mental retardation in Atypical Rett Syndrome. Smad1 silencing, based on RNA interference (RNAi), was performed
in premigratory FNC cells. Soon after electroporation of RNAi molecules, Smad1 inactivation totally abolished the expression of
Foxg1 in the telencephalon, and resulted in dramatic microcephaly and partial holoprosencephaly. Besides, the depletion of Foxg1
activity altered the expression Otx2 and Foxa2 in di/mesencephalic neuroepithelium. However, when mutated forms of
Smad1mediating Fgf and Wnt signaling were transfected into FNC cells, these defects were overcome. We also revealed that Dkk1, a
Wnt antagonist produced by FNC, initiated the specification of the telencephalon by regulating Foxg1 activity. Additionally, the
activity of Cerberus in FNC-derived mesenchyme synergized with Dkk1 to control Foxg1 expression and maintained the balance
between Otx2 and Foxa2. Our present results strongly suggest that some syndromic neurological disorders, which involve
misregulations of Foxg1 and Otx2 are neurocristopathic in origin.
Program/Abstract # 354
The specification of jaw identity in avian embryos
Richman, Joy; Nimmagadda, Suresh; Geetha-Loganathan, Poongodi; Fu, Kathy (University of British Columbia, Canada)
Hox-negative neural crest cells migrate from the brain into the face and give rise to the facial skeleton. With the exception of the joint,
the majority of jaw patterning is determined after neural crest cells reach their destination. Local interactions with the forebrain,
foregut and facial epithelium restrict the fate of cells and specify their identity. We previously identified two signaling pathways that
together specify frontonasal identity, BMP and retinoids. In avian embryos, implantation of beads soaked in Noggin, a BMP
antagonist, and retinoic acid transform maxillary jaw elements to those typical for the midline. A microarray study was carried out and
here we are focusing on the genes upregulated by Nog-RA that may be mediating the change in identity in maxillary mesenchyme.
Peptidase Inhibitor 15 (PI15) is expressed in the normal facial midline and codes for a poorly characterized, secreted protein. We
performed gain and knock-down experiments and determined that PI15 is a mediator of the transformation phenotype and an RA
target. A major part of the phenotype is the formation of cartilage in the palate which necessitates a change in fate of
ectomesenchyme. We found that like Nog-RA, PI15 protein is able to induce a reporter for the chondrogenic program (Sox9-
luciferase). The second striking aspect of the phenotype is the identity change. EMX2, which is normally expressed in the forebrain, is
induced in the maxillary region in Nog-RA treated embryos. We propose that the beak phenotype is due to simultaneous induction of
cartilage and alteration of the maxillary environment to take on characteristics of the mesenchyme adjacent to the forebrain. Funded
by CIHR grants to JMR and a CIHR PDF to SN.
Program/Abstract # 355
Fibulin-7 is expressed in mouse early development and its C-terminal fragment shows anti-angiogenic activity
Forcinito, Patricia (National Institutes of Health, USA); de Vega, Susana (Juntendo University Graduate School of Medicine, Japan);
Yamada, Yoshihiko (National Institutes of Health, USA)
The extracellular matrix (ECM) plays critical roles in many aspects of cellular behavior during development; and in tissue functions,
regeneration, and diseases. The fibulins are a family of secreted glycoproteins associated with other matrices 1 . Mutations on fibulins
have been related to genetic disorders in humans 2 (i.e. limbs malformations, eyes disorders and connective tissue abnormalities). We
previously identified fibulin-7 (Fbln-7) as a new member of the ECM fibulin family 3 . Fbln-7 is expressed in teeth and acts as a cell
adhesion molecule for odontoblasts 3 . Fbln-7 is also expressed in avascular tissues such as cartilage, eyes, and placenta. We found that
the recombinant C-terminal Fbln-7, named fibulistatin, inhibited human umbilical vein endothelial cell (HUVEC) tube formation,
suggesting a role of this fragment in anti-angiogenesis, which plays an essential role in implantation and placentation processes. To
study the role of Fbln-7 in development, we analyzed the expression pattern of Fbln-7 in various stages of mouse development
including the blastocyst stage, the implantation stage, and late embryonic stages. We found that Fbln-7 was expressed in the
extraembryonic tissue at early embryonic tissues and in the placenta at later stages. We also found that Fbln-7 was expressed in the
pregnant female uterus, which normal function is essential for successful implantation and placentation. These results suggest that
Fbln-7 may play a role in peri-implantation, placenta formation and finally, in normal embryonic development.
Program/Abstract # 356
Establishing the border between the Intermediate and Paraxial mesoderm during chick embryonic development
Schneider, Jenny; Yelin, Ronit; Schultheiss, Thomas M. (Technion-Israel Institute of Technology, Israel)
The kidney is a vital organ functioning mainly as the body's excretory system. In vertebrates, all kidney tissue develops from the
intermediate mesoderm (IM), a strip of mesodermal tissue lying between the paraxial mesoderm (PSM) and the lateral plate mesoderm
(LPM). Differentiation of IM cells and their interaction with adjacent PSM cells at early developmental stages are crucial for kidney
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