Multipotent intestinal stem cells maintain the homeostasis and function ofDrosophila intestinal epithelium
A model of Drosophila multipotent intestinal stem cells that use Notch signalling to generate daughter cells with different fates at different times and in different places.
① When Drosophila intestinal stem cells divide in the adult stage, 90% of the division is to produce EB cells that will differentiate into intestinal epithelial cells in the future. At this time, the stem cells strongly activate the Notch signal in EB and promote EB to differentiate into epithelial cells(EC). ② After a certain number of divisions, the stem cells accumulate a sufficient amount of Sc protein, and the endocrine cell differentiation factor Pros begins to be expressed. After asymmetric division, the stem cells divide to produce endocrine progenitor cells (EEP/EMC). At this time, EMC expresses Notch signaling pathway ligand, weakly activates Notch signaling pathway in stem cells, inhibits the expression of Sc, maintains stem cell stemness, and then divides into a pair of endocrine cells. Since stem cells no longer express Sc, they become intestinal stem cells that produce EC, and their fate continues to circulate between ① and ②. ③ When the Notch signal is additionally activated in stem cells and progeny cells, the stem cells differentiate into EC cells. ④When the Notch signaling pathway is mutated in stem cells and progeny cells, ISC-like or ee-like intestinal tumors are formed.
Drosophila intestinal stem cell is an ideal model for studying the number and location of stem cells
Changes in the number of intestinal stem cells of Drosophila in the pupal stage and the division pattern of stem cells.
Left: Model of the number and distribution pattern of stem cells and endocrine cells in the intestine; Right: Model of the division pattern of intestinal stem cells in the pupal stage. A: At 44h APF, the number of stem cells in the intestine is about 600. At this time, the stem cells express the cell polarity protein Mira and the endocrine cell differentiation transcription factor Pros. Under the action of Mira, Pros is collected on the cell membrane on the basal side of stem cells. B: When stem cells divide asymmetrically into two, about 600 stem cells and 600 endocrine cells are distributed in the intestine. At 56h APF, stem cells and endocrine cells each divide symmetrically. Pros is located in the cytoplasm during symmetrical division. C: symmetrical division makes the number of stem cells and endocrine cells in the intestine at 72h APF reach about 1200. Pros protein is located in the nucleus of endocrine cells.
Similarities and differences between asymmetric division of Drosophila neural stem cells and intestinal stem cells
The pattern and molecular mechanism of asymmetric division of Drosophila type 1 neural stem cells and intestinal stem cells.
A: Drosophila type-1 neural stem cells undergo an asymmetrical division during the embryonic stage. The division axis is perpendicular to the "Apical-basal" axis, producing two progeny cells, one large and one small. The large progeny cells at the apical continue to occupy the apical position of the neural stem cells in the outermost ectoderm, maintaining the self-renewal of the stem cells. The daughter cells at the basal differentiate into ganglion blasts (GMC) and then undergo a symmetrical division to produce a pair of nerves. B: The molecular mechanism of the asymmetric division of neural stem cells: (1) Par complex locates to the apical cell membrane to establish an internal polarity axis; (2) Par complex locates Pon and Miranda on the basal cell membrane through phosphorylation, Pon and Miranda are further physically combined to locate Numb, Brat, and Prospero on the basal cell membrane; (3) The Par complex recruits Inscuteable, Pins, Gαi, and Mud to establish a "apical-baasal" mitotic spindle axis; (4) The apical polar protein and the basal cell fate determining factors are distributed asymmetrically in the two daughter cells. C: In the metaphase of asymmetric division of intestinal stem cells, the Par protein complex is located on the apical of the cell membrane, and Miranda and Prospero are located on the basal of the cell membrane, forming a spindle axis perpendicular to the basement membrane. With the progress of mitosis, the spindle axis continuously deflects from the state perpendicular to the basement membrane until it is parallel to the basal membrane at the end of division. After the mitotic cytoplasm is separated, the progeny cells originally located at the apical of the metaphase return to the basal membrane and become stem cells that continue to renew themselves. Prospero protein enters the nucleus of the progeny cells originally located at the basal, allowing the progeny cells to differentiate into endocrine cells.