Previous studies suggest that the risk of nonsyndromic cleft lip with or without cleft palate (CL±P) and isolated cleft palate (CP) is influenced by genetic variation at several loci and that the relation between specific genetic variants and disease risk may be modified by environmental factors. The present study evaluated potential associations between CL±P and CP and two putative clefting su...

Conversions of signaling gradients into sharp "all-or-none" borders are fundamental to tissue and organismal development. However, whether such conversions can be meaningfully reduced to dissociated cells in culture has been uncertain. Here we describe ultrasensitivity, the phenomenon equivalent to an all-or-none response, in dissociated neural precursor cells (NPCs) exposed to bone morphogenet...

Transcription factors PAX9 and MSX1 play crucial roles in the development of permanent teeth at the bud stage, and their loss-of-function variants have been associated with congenital tooth agenesis. We sequenced the coding regions of the PAX9 and MSX1 genes from nine patients with non-syndromic tooth agenesis, and identified a missense mutation, P20L, of PAX9 in a single familial case involvin...

Failure to develop complete dentition, tooth agenesis, is a common developmental anomaly manifested most often as isolated but also as associated with many developmental syndromes. It typically affects third molars or one or few other permanent teeth but severe agenesis is also relatively prevalent. Here we report mutational analyses of seven candidate genes in a cohort of 127 probands with non...

Type A1 brachydactyly in humans is a recognisable syndrome characterised by shortening of the middle phalanx of all digits with occasional fusion of the middle and terminal phalanges. The purpose of this study was to evaluate candidate genes for type A1 brachydactyly in two families with multiple affected members. Several classes of genes have been implicated in the control of distal limb devel...

The observation that certain patterns of tooth agenesis occur more frequently in individuals of the same family may suggest the existence of predisposing genetic factors. The aim of this study was to search for mutations in the PAX9 and MSX1 genes and to investigate their potential association with the maxillary lateral incisor agenesis (MLIA) phenotype in 12 Portuguese families, a total of 52 ...

Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. With the large number of genes involved in the odontogenesis process, the opportunity for mutations to disrupt this process is high. Mutational analysis has revealed genes that are major causes of non-syndromic hypodontia. The most common permanent missing teeth are the third molars, second premolars, ...

BACKGROUND Congenital dental anomalies can affect up to 25% of the population. AIM To report the genetic study of a family with dental anomalies. MATERIAL AND METHODS We studied a Chilean family presenting with three independent dental phenotypes: third molar agenesis, supernumerary teeth, and dentinal dysplasia type I. We searched for mutations in candidate genes proposed for tooth agenesi...

Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/beta-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for norm...

Patterning of the dorsal neural tube involves Bmp signaling, which results in activation of multiple pathways leading to the formation of neural crest, roof plate and dorsal interneuron cell types. We show that constitutive activation of Bmp signaling at early stages (HH10-12) of chick neural tube development induces roof-plate cell fate, accompanied by an increase of programmed cell death and ...