Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway

• Published in: Developmental biology Vol. 353; no. 2; pp. 161 - 172
• Main Authors: Takashima, Shigeo, Adams, Katrina L., Ortiz, Paola A., Ying, Chong T., Moridzadeh, Rameen, Younossi-Hartenstein, Amelia, Hartenstein, Volker
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.2011
• Subjects: adults; Animals; Animals, Genetically Modified; Cell Differentiation; Cell Lineage; Cell Proliferation; Drosophila; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endocrine System - embryology; Endocrine System - growth & development; Endocrine System - metabolism; Enteric Nervous System - embryology; Enteric Nervous System - growth & development; Enteric Nervous System - metabolism; Entero-endocrine cell; enterocytes; Enterocytes - cytology; Enterocytes - metabolism; Female; Intestinal Mucosa - metabolism; Intestines - embryology; Intestines - growth & development; Intracellular Signaling Peptides and Proteins; larvae; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Midgut; Models, Biological; Morphogenesis; Neurogenesis; Notch; population size; Receptors, Notch - genetics; Receptors, Notch - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Signal Transduction; Stem cell; stem cells; Entero-endocrine cell; Midgut; Stem cell; Drosophila; Notch
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2011.01.039

In this paper we have investigated the developmental–genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells. ► Development of intestinal endocrine cells was studied in embryo, larva, and pupa of Drosophila. ► In all stages, a progenitor/stem cell population produces the endocrine cells in a similar manner. ► Delta/Notch signaling is found to be crucial for restricting the endocrine cell population.