While some of the signaling molecules that govern establishment of the limb axis have been characterized, little is known about the downstream effector genes that interpret these signals. In Drosophila, the spalt gene is involved in cell fate determination and pattern formation in different tissues. We have cloned a chick homologue of Drosophila spalt, which we have termed csal1, and this study...

To the Editor : Mutations of the GLI3 gene lead to a wide variety of phenotypes such as Greig cephalopolysyndactyly (GCPS), Pallister–Hall syndrome (PHS), postaxial polydactyly (PAP) types A/B, and preaxial polysyndactyly (PPD) type IV (1–7). The main clinical features of these phenotypes are summarized in Table 1. The GLI3 protein may be divided into three parts (Fig. 1). The part towards the ...

Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant ...

LetK/Qp be a finite extension and GK = Gal(K̄/K) the Galois group of an algebraic closure K̄. Let F be a finite field of characteristic p, and VF a finite dimensional F-vector space equipped with a continuous action of GK . The study of the deformation theory of Galois representations was initiated by Mazur [Ma], who showed that if VF has no non-trivial endomorphisms, then it admits a universal d...

1: Overview of main results. 2: The eigencurve via Galois representations. 3: Classification of crystalline Galois representations. (2 lectures). 4: Construction of potentially semi-stable deformation ring (2 lectures). 5: Modularity of potentially Barsotti-Tate representations. 6: The Fontaine-Mazur conjecture for GL2 (2 lectures). Recall the statement of the Fontaine-Mazur conjecture, which s...

Critical functional properties are embedded in the non-coding portion of the human genome. Recent successful studies have shown that variations in distant-acting gene enhancer sequences can contribute to disease. In fact, various disorders, such as thalassaemias, preaxial polydactyly or susceptibility to Hirschsprung's disease, may be the result of rearrangements of enhancer elements. We have a...

An enhancer named MFCS1 regulates Sonic hedgehog (Shh) expression in the posterior mesenchyme of limb buds. Several mutations in MFCS1 induce ectopic Shh expression in the anterior limb bud, and these result in preaxial polydactyly (PPD). However, the molecular basis of ectopic Shh expression remains elusive, although some mutations are known to disrupt the negative regulation of Shh expression...

The intracellular target of diphtheria toxin is a modified histidine residue, diphthamide, in the translation elongation factor, eEF2 (also known as EFT1). This enigmatic modification occurs in all eukaryotes and is produced in yeast by the action of five gene products, DPH1 to DPH5. Sequence homologues of these genes are present in all sequenced eukaryotic genomes and, in higher eukaryotes, th...

Illusory motion reversal does not imply discrete processing: Reply to Rojas et al. Under certain conditions a smoothly moving pattern viewed under continuous light is sporadically perceived to The existence of this surprising illusion has been taken as evidence that the visual system takes discrete snapshots of the visual scene In our previous work we have provided evidence against this supposi...

Crucial roles for T-box3 in development are evident by severe limb malformations and other birth defects caused by T-box3 mutations in humans. Mechanisms whereby T-box3 regulates limb development are poorly understood. We discovered requirements for T-box at multiple stages of mouse limb development and distinct molecular functions in different tissue compartments. Early loss of T-box3 disrupts...