Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Insulin/insulin-like growth factor (IGF) signaling constitutes an evolutionarily conserved pathway that controls growth, energy homeostasis, and longevity. In Drosophila melanogaster, key components of this pathway are the insulin-like peptides (Dilps). The major source of Dilps is a cluster of large neurons in the brain, the insulin-producing cells (IPCs). The genetic control of IPC development and function is poorly understood. Here, we demonstrate that the Pax6 homolog Eyeless is required in the IPCs to control their differentiation and function. Loss of eyeless results in phenotypes associated with loss of insulin signaling, including decreased animal size and increased carbohydrate levels in larval hemolymph. We show that mutations in eyeless lead to defective differentiation and morphologically abnormal IPCs. We also demonstrate that Eyeless controls IPC function by the direct transcriptional control of one of the major Dilps, dilp5. We propose that Eyeless has an evolutionarily conserved role in IPCs with remarkable similarities to the role of vertebrate Pax6 in beta cells of the pancreas.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





16183 - 16188


Animals, Base Sequence, Cell Differentiation, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Eye Proteins, Female, Gene Expression Regulation, Developmental, Homeodomain Proteins, Inhibitor of Apoptosis Proteins, Insulin, Insulins, Male, Molecular Sequence Data, Mutation, Neurons, PAX6 Transcription Factor, Paired Box Transcription Factors, Repressor Proteins, Signal Transduction, Transcription, Genetic