Non-apical mitoses contribute to cell delamination during mouse gastrulation.

During the epithelial-mesenchymal transition driving mouse embryo gastrulation, cells divide more frequently at the primitive streak, and half of those divisions happen away from the apical pole. These observations suggest that non-apical mitoses might play a role in cell delamination. We aim to uncover and challenge the molecular determinants of mitosis position in different regions of the epiblast through computational modeling and pharmacological treatments of embryos and stem cell-based epiblast spheroids.

Origin and flow-mediated remodeling of the murine and human extraembryonic circulation systems.

The transduction of mechanical stimuli produced by blood flow is an important regulator of vascular development. The vitelline and umbilico-placental circulations are extraembryonic vascular systems that are required for proper embryonic development in mammalian embryos. The morphogenesis of the extraembryonic vasculature and the cardiovascular system of the embryo are hemodynamically and molecularly connected.

A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

ATP-sensitive potassium (K[ATP]) channels are an essential component of glucose-dependent insulin secretion in pancreatic islet beta-cells. These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family.

Mapping novel pancreatic islet genes to human chromosomes.

A strategy was developed to generate expressed sequence tags (ESTs) from human pancreatic islet gene products using differential display of mRNA. Screening of over 2,000 cDNA amplification products identified 42 cDNAs that were preferentially expressed in pancreatic islets relative to exocrine tissue. Public database analysis showed that 29 (69%) corresponded to novel genes, in contrast with only 66 of 250 (26.

Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (I) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (delta F1388) and (II) a previously described g-->a transition at position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a).