06-P050 Wnt antagonists regulate urethra tubercularization and cloaca septation

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MECHANISMS OF DEVELOPMENT

1 2 6 (2 0 0 9) S1 2 0–S 13 6

The role of FGFRL1 as a decoy receptor in the FGF signalling

1

The University of Hong Kong, Hong Kong, China

pathway provides a new entry in the study of FGF signal transduc-

2

China Medical University, Shenyang, China

tion pathways and in the role of FGF signalling in development and disease.

In early vertebrate embryos, a ventral-caudal midline cloaca canal exists linking the urinary and intestinal streams. Later in

doi:10.1016/j.mod.2009.06.273

development, the cloaca is septated by complex endodermally lined mesenchymal foldings (Tourneux and Rathke folds), resulting in the formation of the urethra and separation of urinary from anorectal systems. Disruption of these folding and septation pro-

06-P048 Investigating the basis of foregut and lung abnormalities in a mouse model of human congenital malformations Piotr Hajduk

1,2

2

, Prem Puri , Paula Murphy

1

cesses results in either anorectal malformations (ARMs) or hypospadias. Approximately 14% of patients with ARMs also exhibit hypospadias, suggesting dysregulation of common signaling pathway(s) could give rise to both conditions.

1

To investigate the molecular changes associated with ARMs

2

and the possibilities of the associations between hypospadias

Zoology Department, Trinity College Dublin, Dublin, Ireland Children’s Research Centre, Crumlin Hospital, Dublin, Ireland

and ARMs, microarray analysis was performed to identify differOesophageal atresia/Tracheo-oesophageal fistula (OA/TOF) are

entially expressed genes between ETU-treated and normal rat

common congenital malformations of the foregut in newborns.

embryos at E14.5. ETU is a well-established drug to induce ARMs

Until recently little was known about the pathogenesis of these

in rat fetuses by intragastric administration to pregnant rats.

anomalies. Adriamycin, a chemotherapy agent, has been found

Array analysis and subsequent confirmation by real-time RT-

to cause birth defects in mice that resemble the OA/TOF anoma-

PCR in biological replicates revealed upregulation of two genes

lies providing an animal model to study the etiology of the

encoding Wnt antagonists in ETU-treated embryos. ETU-treated

defects. A number of genes have been implicated in regulating

embryos displayed urorectal developmental defects typified in

normal development of the trachea and oesophagus where muta-

human hypospadisis and ARMs including delayed genital devel-

tions in mice cause abnormal development. This project exam-

opment, untubularized penile urethra, as well as the presence

ines the possible involvement of such candidate genes in the

of internal fistula of vagina to rectum and urethra. Immuno-his-

Adriamycin-treated mouse model.

tochemical analysis on E14.5–E16.5 rat embryos revealed that

Optical projection tomography (OPT) is a 3D imaging tech-

Wnt antagonists were highly expressed at the ventral cloaca

nique that allows visualisation of gene expression patterns in

canal, ventral urethral endoderm and anal opening. Taken

the anatomical context of the embryo allowing changes in gene

together all these data suggest that Wnt antagonists are involved

expression to be related to alterations in morphological events.

in the early urogenital and anorectal developments, and dysregu-

Genes involved in cell communication systems integral to lung

lation of Wnt signaling in embryos could result in defective uro-

and foregut development are been examined in this way.

rectal development.

Time-mated CBA/Ca mice received intraperitoneal injections of adriamycin (6 mg/kg) or saline on day 7 and 8 of gestation. Embryos

doi:10.1016/j.mod.2009.06.276

were harvested on days 9–12 and stained following whole mount insitu hybridization with labeled RNA probes to detect specific gene transcripts. Immunohistochemistry using an antibody specific to

06-P051

endoderm cells (Hnf3b) was used to visualize morphology.

Mechanisms of spina bifida in the Zic2-Kumba mouse

Among the genes under analysis is Tbx4 a member of the fork-

Saba Raza, Valentina Massa, Nicholas Greene, Andrew Copp

head family of transcription factors involved in spatial patterning of mesoderm differentiation. The temperospatial expression of

Institute of Child Health, London, United Kingdom

Tbx4 during the critical period of separation of the trachea and oesophagus in normal and adriamycin treated embryos was revealed.

Bending of the neural plate is essential for neural tube closure in mammals. Studies in mice have shown that the precise mode of bending varies according to the axial level: rostrally, a single

doi:10.1016/j.mod.2009.06.274

median bending point occurs, whereas caudally, paired dorsolateral bending points are formed. A failure of dorsolateral bending in the spinal neural tube of the Kumba mouse (Zic2Ku/Ku), which has loss-of-function alleles of the Zic2 gene, leads to spina bifida.

06-P049

Dorsolateral bending is the ‘default’ mechanism of neural tube

– Withdrawn

closure, and is regulated by a complex signalling network involving bone morphogenetic proteins (BMPs). BMP signalling is necessary and sufficient to inhibit dorsolateral neural plate bending in

06-P050

mice, whilst BMP antagonists such as noggin and neuralin are

Wnt antagonists regulate urethra tubercularization and cloaca

necessary and sufficient to induce dorsolateral bending. Since

septation

noggin and neuralin expression are both reduced in the dorsal

Roy Chun Laam Ng1, Vincent Chi Hang Lui1,

neural tube of Zic2Ku/Ku embryos, and phospho-Smad1,5,8

Maria-Mercedes Garcia-Barcelo1, Zheng Wei Yuan2,

expression is elevated, it appears that the BMP signalling pathway

Paul Kwong Hang Tam1

is perturbed in Zic2Ku/Ku embryos. We have run a microarray to