Introduction

Welcome to the Horb lab. We are situated in the heart of Montreal at the Clinical Research Institute of Montreal (IRCM). Research in this lab is focused on identifying the molecular mechanisms underlying cell fate specification during organogenesis.

The lab uses the amphibian, Xenopus laevis, as its model organism to identify the master switch genes involved in endodermal organ development. It has been commonly assumed that as embryogenesis proceeds cells become irreversibly restricted in their cell fates. Recent work, however, has shown that there is much more plasticity in cellular differentiation, such that transdifferentiation between cell types is possible.

The endoderm is one of the three primary germ layers that is formed during gastrulation. Cells derived from the endoderm give rise to the gastrointestinal and respiratory tracts, including the pancreas, liver and lungs. Embryonic development of the endoderm occurs in three stages: formation, regional specification and differentiation. First, the endodermal germ layer is established cell-autonomously during gastrulation through the work of maternally localized determinants, such as VegT. Second, patterning of the endoderm subsequently occurs through signals emanating from the mesoderm that subdivides the endoderm into anterior/posterior, dorsal/ventral and right/left axes. Finally, cell fate becomes irreversibly determined through the interactions of various intracellular transcription factors. While our knowledge of endoderm formation has increased in recent years, much more work is needed to understand the molecular signals involved in specification and differentiation of the various endodermal organs, including the pancreas, liver and lungs.

Work in the lab is interested in elucidating the molecular signals involved in the last two steps, namely specification and differentiation of the endoderm. The current research projects include: