Abstracts - Society for Developmental Biology

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(Queens College, Flushing, United States); Leung, Alanna (Townsend Harris High School, Flushing, United States);
Karp, Ariel (Queens College, Flushing, United States); Singleman, Corinna (Queens College, CUNY Biology, United
States)
Cardiac morphogenesis is a tightly orchestrated dance between cardiac form and function. Cardiomyocytes begin to
contract well before a complete heart tube forms and these contractions are fundamental to generating flow through the
heart. This flow is detected as shear stress within the heart and directs further morphogenesis of the heart thus changing the
flow patterns and continuing the cycle. We have identified a dominant zebrafish mutant in the atrial specific myosin myh6.
Interestingly, this mutation results in modified blood flow leading to two distinct mutant phenotypes; an overly muscular
heart that becomes constricted or a dilated myocardium. Close examination of these cardiomyopathies demonstrated two
divergent contractility phenotypes; a non-contracting atrium and partially-contracting atrium. In the non-contracting
mutants, the heart constricts, reducing the amount and efficiency of blood flow, resulting in death at around 5 days post
fertilization. Partial-contractility results in embryos with a dilated myocardium, both in the atrium and ventricle, yet the
majority of these fish are viable and live to adulthood with ongoing defects in cardiac form and presumably function. We
are currently examining the blood flow and sheer stresses in myh6 mutants during early development and are conducting
micro-array analysis to identify genes involved in initiating these two distinct phenotypes. We expect these studies to
further develop the use of the myh6 mutants as a model for cardiomyopathy and generate an understanding of the
molecular regulation of these divergent cardiomyopathies.
Program/Abstract # 120
Myocardial progenitors in the pharyngeal regions migrate to distinct conotruncal regions
Nakajima, Yuji; Takahashi, Makiko; Terasako, Yumi; Yanagawa, Nariaki; Kai, Masatake; Yamagishi, Toshiyuki, Osaka
City Univ Med Sch, Japan
The cardiac progenitor cells for the heart outflow tract (OFT) reside in the visceral mesoderm of the pericardial coelom
caudal to the developing OFT and mesodermal core of the anterior pharyngeal arches, which are defined as the SHF
(secondary heart field) and AHF (anterior heart field), respectively. Although SHF/AHF is known to contribute to form
conotruncal region, the destination of progenitor cells reside in each second lineage of heart forming region is not clarified.
Using chick embryos, we injected fluorescent-dye into the SHF or AHF at stage 14 (ED 2), and the destinations of the
labeled cells were examined at stage 31 (ED 7) by fluorescent stereoscopic microscope. To further examine, hearts were
fixed, serial sections were cut, stained with anti-sarcomeric α-actinin and defined the distribution of the labeled cells. Dyelabeled
cells from the right SHF were found in the α-actinin-positive myocardium on the left dorsal side of the OFT, and
cells from the left SHF were detected on the right ventral myocardium of the OFT. Dye-labeled cells from the right and left
AHF in the anterior two pairs of pharyngeal arches migrated to regions of the ventral wall of the OFT close to the aortic
and pulmonary valves, respectively. These observations indicate that myocardial progenitors from the SHF and AHF
contribute to distinct conotruncal regions, and that cells from the SHF migrate rotationally into the OFT while cells from
the AHF in a non-rotational manner. Results suggest that spatiotemporal abnormal development in each of second lineage
of heart forming regions may cause the specific spectrum of conotruncal heart defects.
Program/Abstract # 121
Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-kappaB
Voutilainen, Maria; Lindfors, Päivi; Lefebvre, Sylvie; Ahtiainen, Laura; Fliniaux, Ingrid; Rysti, Elisa; Murtoniemi, Marja
(University of Helsinki, Helsinki, Finland); Schneider, Pascal (University of Lausanne, Epalinges, Switzerland); Schmidt-
Ullrich, Ruth (Center for Molecular Medicine, Berlin,, Germany); Mikkola, Marja (University of Helsinki, Helsinki,
Finland)
The mammary gland development begins during embryogenesis but is only completed during adulthood. Whereas the
hormone dependent ductal growth during adulthood has been extensively studied relatively little is known about the
molecular pathways controlling the early stages of ductal growth. Ectodysplasin (Eda), a member of the tumor necrosis
factor family, is one of the regulators of skin appendage development in vertebrates. In activating mutations in Eda lead to
hypohidrotic ectodermal dysplasia, which is characterized by hair abnormalities, missing teeth, and inability to sweat. The
function of Eda in mammary gland development has not been studied in detail. We have previously shown that transgenic
overexpression of Eda in developing ectoderm (K14-Eda mice) leads to formation of ectopic mammary placodes. Here we
report that NF-kB, downstream of Eda, is a novel regulator of embryonic and pre-pubertal mammary ductal
morphogenesis. Excess of Eda caused precocious and accelerated branching morphogenesis that was NF-kBdependent.The
opposite was seen with loss of Eda or inhibition of NF-kB which led to ductal trees with fewer branches.
We have identified PTHrP, Wnt10a and Wnt10b, two Egf-family ligands (amphiregulin and epigen), as putative
transcriptional targets of the Eda/NF-kB pathway. Using an ex vivo embryonic mammary bud culture system that we have