Transcriptional control of pancreatic endocrine cell development.
In diabetes mellitus, insulin-producing beta cells in the pancreas are lost (type 1) or dysfunctional (type 2). Cell replacement therapy has emerged as a promising alternative to insulin injection for treatment of diabetic patients. Given the scarcity and difficulty in obtaining pancreatic beta cells from cadaveric donors, current research is aiming at the generation of functional beta cells from non-beta-cell sources or from pluripotent progenitors such as adult or embryonic stem cells. However, to achieve this, we first need to understand how beta cells are formed during normal development. Knowledge of the molecular and genetic pathways that direct cells along their differentiation pathway will be instrumental if we aim to engineer new beta cells for clinical use. This article reviews pancreatic development from a gene expression point of view and discusses our current understanding of the transcription factors that rule pancreatic morphogenesis during ontogeny.
Gasa
Rosa
R
Laboratori de Diabetis Experimental, IDIBAPS, Barcelona, Spain. rgasa@clinic.ub.es
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000502:physiology; D010179:Pancreas / Q000196:embryology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490003:MNX1 protein, human; C498695:NEUROG3 protein, human; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1