Table 1.

Genes required for endocrine development

GeneIslet cell types affected in knockoutReferences
Core endocrine program
Is/1 All (absent) Ahlgren et al., 1997
NeuroD All (reduced) Naya et al., 1997
Insm1/IA1 α-, β- and δ-cells (reduced) Gierl et al., 2006
Islet subtype specification
Pax6 α-, β- and δ-cells (reduced); ϵ-cells (increased)Heller et al., 2005; Sander et al., 1997
Pax4 β-cells (strongly reduced); δ-cells (absent); α-cells (increased)Collombat et al., 2005; Sosa-Pineda et al., 1997
Arx α-cells (absent); β- and δ-cells (increased) Collombat et al., 2003
Nkx2.2 β-cells (absent); α- and PP-cells (reduced); ϵ-cells (increased)Sussel et al., 1998; Wang et al., 2004
Nkx6.1 β-cells (absent) Sander et al., 2000
Hlxb9 β-cells (reduced)Harrison et al., 1999; Li et al., 1999
Foxa2 α-cells (strongly reduced) Lee et al., 2005
  • Genetic analyses implicate these genes in various aspects of islet development, either acting in a general program that generates most or all endocrine cells, or to promote the development of specific endocrine cell subtypes. As indicated, the latter class includes genes whose deletion phenotype causes decreases in one or more cell types balanced by increases in others, indicating that they act to bias the cell fate decision of a multipotent progenitor. Not listed are genes whose deletion compromises islet cell function, without preventing specification or differentiation.