Abstracts - Society for Developmental Biology

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involved in Drosophila ventral furrow formation. We have shown that bgm is transcriptionally regulated by products of the
patterning genes dorsal, twist and snail, each critical to formation of the mesoderm. In turn, bgm likely contributes to the
maintenance of optimal levels of cellular very long chain fatty acids and thus to cellular cytoarchitecture. We have shown
using in situ hybridization studies that bgm transcripts are expressed in the ventral furrow forming cells. Importantly, in
embryos lacking both maternal and zygotic contributions of bgm, cells undergoing ventral furrow formation move in an
uncoordinated fashion and the embryos fail to gastrulate. Thus, our studies have identified a prominent molecular player in
gastrulation.
Program/Abstract # 450
Timing of southpaw initiation in lateral plate mesoderm is altered in ccdc40 and pkd2 morphants
McSheene, Jason; Burdine, Rebecca, Princeton University, Princeton, United States
Pkd2 is a geneimplicated in human Autosomal Dominant Polycystic Kidney Disease. In addition to kidney defects,
mutations and knockdowns of pkd2 in mouse and zebrafish disrupt normal left-sided nodal expression in the lateral plate
mesoderm (LPM). Although pkd2 has been shown to be important in creation and initial restriction of nodal expression
domains to the left LPM, the link between pkd2 and the initiation of nodal expression is unknown. To probe the functions
of PKD2 in embryonic left-right patterning we examined the effects morpholino knockdown of the gene has on the timing
of the zebrafish nodal-related gene southpaw expression in the LPM. PKD2 protein appears to be important for correct
timing of propagation of southpaw expression as well as unilateral restriction. Interestingly, knockdown ofCCDC40, a
protein involved in correct cilia assembly and rotation, results in randomized expression of nodal in the LPM and a similar
delay in southpaw expression. We use this approach of southpaw expression timing to elucidate the functions of different
proteins in their roles establishment of left-right asymmetry.
Program/Abstract # 451
The Integrator Complex Subunit 6 is a negative regulator of the vertebrate organizer
Kapp, Lee D.; Abrams, Elliott; Marlow, Florence; Mullins, Mary, Univ of Pennsylvania School of Medicine,
Philadelphia, United States
Dorsal-ventral patterning relies upon the mutual antagonism of competing signaling pathways to establish a balance
between ventralizing BMP signaling and dorsal fate specification mediated by the organizer. In zebrafish, the initial
embryo-wide domain of BMP signaling is refined into a morphogenetic gradient following activation of a maternal
Wntpathway leading to nuclear accumulation of β-cateninon the dorsal side of the embryo, repression of BMP signaling
dorsally, and theinduction of dorsal fates mediated by the Nodal and FGF signaling pathways. Incontrast, the Wnt8
pathway operating zygotically limits dorsal fatespecification and maintains the specification of ventrolateral nonaxialmesoderm.
We have isolated a recessive dorsalizing maternal-effect mutation affectingthe Integrator Complex Subunit
6 (Ints6), a member of a complex whose only reportedrole is to mediate 3’ end processing of spliceosomal snRNAs. Due to
widespread de-repression of dorsalizing genes, embryos born to mutant mothers fail to maintain expression of
BMPligands, fail to maintain operation of the Wnt8 pathway, display delayed cell movements during gastrulation, and
become severely dorsalized. Limitation of Nodalsignaling or the restoration of BMP signaling completely rescues the
patterningof affected embryos. Preliminary data indicate that Ints6 is required on thedorsal side of the embryo to restrict
organizer gene expression. We are engaged in experiments to determine if snRNA processing is affected in mutant
embryos. Furthermore, we hope to determine whether Ints6 participates in embryonic patterning independently of the
Integrator Complex or whether our data indicatea new role for this RNA processing machine.
Program/Abstract # 452
PIAS-like protein Zimp7 is required for Zebrafish organizer formation and dorsal mesoderm development
Moreno, Roberto; Schnabel, Denhi; Salas, Enrique; Lomelí, Hilda, Institute of Biotechnology, National Autonomous
University of Mexico, Cuernavaca, Mexico
Human ZIMP7 protein and its homolog ZIMP10 were initially identified as androgen receptor co-activators. Analysis of
their sequence revealed the presence of an SP-RING/Miz domain, which is highly conserved in members of the PIAS
family and confers SUMO-conjugating activity. The ZIMP proteins also interact with transcription factors such as p53 or
Smad3/Smad4 and with BRG1, the catalytic subunit of the SWI-SNF remodeling complex. Accordingly tonalli, the
drosophila orthologue of the Zimp genes, was shown to interact with subunits of the Brahma complex. Mutations in tonalli
produce flies with homeotic phenotypes. In zebrafish zimp7 is ubiquitously expressed in embryos from one-cell up to bud
stage. In this study we set out to analyze the role of zygotic Zimp7 in the early stages of zebrafish development. We found
evidence indicating that Zimp7 is required for the formation of the dorsal organizer and for dorsal mesoderm development.
The dorsal organizer is a structure that acts as an inducer of dorsal cell fates and as a regulator of dorsoventral axis