of HED patients could be rescued with EDA treatment, but that

EDA would have to be administered early in development at a

defined concentration for SG rescue to be successful.

doi:10.1016/j.mod.2009.06.266

06-P041

Effects of hypoxia on myogenesis and muscular differentiation in

Xenopus laevis

Magdalena Hidalgo1,2, Thierry Launay1, Thierry Darribre2,

Jean-Paul Richalet1, Michle Beaudry1

1Universit Paris 13 – EA2362 – UFR-SMBH, Bobigny, France2UMR-CNRS 7622 – Biologie du Dveloppement, Paris, France

Mechanisms implied in tissues response to the oxygen partial

pressure remain poorly understood as well as the role of hypoxia

in developmental processes. However, the activation of transcrip-

tion factors such as FoxO and HIF and the recruitment of signal-

ling pathways including Calcineurin, PI3K, p38-MAPK and mTOR

are known to be involved in hypoxia responses. Currently, little

information is known about the involvement of signalling path-

ways generated by these proteins during development. Neverthe-

less, HIF deficiency in mouse leads to a developmental delay,

diseases in neural ridges and placenta formation leading to an

early lethality, and fewer somites.

In vertebrates, somites segment and subdivide to form the

dermomyotome that give the dermis and skeletal muscles. Under

the influence of MyoD and Myf5, myotomal cells differentiate in

myoblastes. Plasmalems fuse under the influence of Myogenin,

to form a myotube that will differentiate in muscle fibre with

the expression of MRF4.

To understand hypoxia influences during myogenesis and to

identify the involved signalling pathways, a developmental model

(Xenopus laevis) was used. Analyses of embryos indicate that

hypoxia play a role in the survival and the embryonic growth with-

out affecting the formation of somites. However, a decrease in the

expression of the muscular markers 12/101 and F59 highlights a

default in the differentiation of myotome cells. These results indi-

cate that the oxygen could be involved in a signalling pathway that

controls the myogenic differentiation during early development.

doi:10.1016/j.mod.2009.06.267

06-P042

Tshz3 deficiency causes functional renal tract obstruction by

impeding ureteric smooth muscle differentiation

Martin Elise1,2, Lye Claire3, Caubit Xavier1, Vola Christine1,2,

Cor Nathalie1, Woolf Adrian3, Schedl Andreas4, Fasano Laurent1

1Developmental biology institute of Marseilles Luminy, Marseille, France2Universit de la Mditerrane, Marseille, France3Nephro-Urology unit, UCL Institute of child health, London, United

Kingdom4Inserm UMR 636, Nice, France

The ureter plays a pivotal role in the urinary system. After fill-

ing the renal pelvis with urine, the upper portion of the ureter

undergoes peristaltic contractions to propel urine down to the

bladder. To ensure this essential function, proper differentiation

of mesenchyme surrounding the urothelium into smooth muscle

(SM) has to be achieved prior urine production starts at E15. Tea-

shirt (Tshz) genes encode zinc finger transcription factors, which

orchestrate embryonic development. Mouse ureteric smooth

muscle cell precursors express Teashirt-3 (TSHZ3) and Tshz3 null

mutant mice have congenital hydronephrosis not associated with

evident anatomical obstruction. Furthermore, in null mutant

embryos, a failure of ureteric SM differentiation antedated the

urinary tract dilatation and implicated TSHZ3 as model of ‘func-

tional’ urinary tract obstruction (Caubit etal., 2008). To identify

new factors involved in renal tract development and to profile

gene networks active in this process, we sought to identify pro-

tein partners of TSHZ3 with a yeast two-hybrid screen. Among

the positive clones, SOX9 was identified as a protein binding part-

ner. Finally, we observe that SOX9 is expressed in an overlapping

expression pattern with TSHZ3 and that Sox9 expression is main-

tained in Tshz3 mutant ureter. The closely overlapping expres-

sion patterns of TSHZ3 and SOX9 suggest a role for SOX9 in

ureter development. We are investigating of the relevance of

TSHZ3 and SOX9 interaction during the ureter morphogenesis.

doi:10.1016/j.mod.2009.06.268

06-P043

Regulation of planar cell polarity signalling by the prenylation

pathway

Masatake Kai1, Nina Buchan1, Carl-Philipp Heisenberg2,

Masazumi Tada1

1University College London, London, United Kingdom2Max Planck Institute of Molecular Cell Biology and Genetics, Dresden,

Germany

During vertebrate gastrulation, the body axis is established by

a variety of co-ordinated and directed movements of cells. One of

these movements is convergence and extension (CE), which is

regulated by a non-canonical Wnt/planar cell polarity (PCP) path-

way. From our forward genetic screen, we have identified 3-

hydroxy-3-methyglutaryl-coenzyme A reductase 1b (hmgcr1b)

gene as a dominant enhancer of the silberblick (slb)/wnt11 CE

phenotype. hmgcr1b mutant embryos exhibit only very mild CE

phenotype during gastrulation while showing a thicker yolk

extension at pharyngula stages. Notably, abrogation of hmgcr1b

also enhances the CE defects of other core PCP mutants/mor-

phants. The prenylation pathway is one of branches downstream

of HMGCR, and has been implicated for lipid modification at the

C-terminus of proteins. To test the possibility that the prenylation

pathway regulates activities of the PCP pathway, we abrogated

farnesyl transferase (FT) or geranylgeranyl transferase (GGT)

function using morpholinos on PCP mutant/morphant back-

grounds. Consistent with the notion that FT preferentially per-

forms lipid modification on to proteins with the CAAX motif

including the core PCP protein Prickle (Pk), abrogation of FT, but

not GGT, enhances the pk1a or pk1b morphant CE phenotype,

suggesting the specif icity for targets of the prenylation enzymes.

doi:10.1016/j.mod.2009.06.269

S132 M E C H A N I S M S O F D E V E L O P M E N T 1 2 6 ( 2 0 0 9 ) S 1 2 0 – S 1 3 6