Polarity is destiny

Abstract

The GTPase Cdc42 specifies polarity in various biological processes. Kesavan et al. (2009) now demonstrate that Cdc42 also regulates epithelial cell polarity in the developing mouse pancreas, where it is required for tubule formation and maintenance. Furthermore, the polarization of epithelial tissue influences the differentiation of pancreatic progenitor cells, linking cell polarity to cell specification.

Figure 1. Cdc42 regulates epithelial structure in pancreas

Cdc42 regulates tubule formation in the pancreas. Tubes form in the developing mouse pancreas through expansion and fusion of existing micro-lumens. At embryonic day 11 and 12 (E11–E12), micro-lumens with visible apical surfaces (blue) form within the pancreas. At E12.5, these micro-lumens start to coalesce into tubular structures. This process requires activation of atypical protein kinase C (aPKC), a downstream effector of the master polarity protein, Cdc42. Between E12.5 and E15.5, luminal structures, which are generated from the micro-lumens, coalesce and mature to form a single layer of polarized epithelium inside the mouse pancreas. Tissue-specific loss of Cdc42 results in fragmented pancreatic epithelia and large cellular aggregates that lack tubules. Furthermore, the failure to establish proper tissue structure in the pancreatic epithelia lacking Cdc42 causes the aberrant differentiation of pancreatic progenitor cells and interferes with cell specification in the developing pancreas.