TY - JOUR
T1 - Stem cell-based growth, regeneration, and remodeling of the planarian intestine
AU - Forsthoefel, David J.
AU - Park, Amanda E.
AU - Newmark, Phillip A.
N1 - Funding Information:
We would like to thank Dr. Tingxia Guo for initial optimization of labeled dextran feeding to planarians, Drs. Tingxia Guo and Francesc Cebrià for generation and initial characterization of the preimmune serum labeling planarian muscles, and Forrest Waters for technical assistance with analysis of proliferation in regenerating tissue fragments. We are grateful to Drs. Jim Collins, Rachel Roberts-Galbraith, Ryan King, and James Sikes for critical readings of this manuscript, and all members of the Newmark Lab for insightful discussions. This work was supported by a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health ( F32-DK077469 ) to DJF and R01-HD043403 to PAN. PAN is an investigator of the Howard Hughes Medical Institute.
PY - 2011/8/15
Y1 - 2011/8/15
N2 - Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by co-ordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context.
AB - Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by co-ordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context.
KW - Intestine
KW - Neoblast
KW - Organogenesis
KW - Planarian
KW - Regeneration
KW - Remodeling
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U2 - 10.1016/j.ydbio.2011.05.669
DO - 10.1016/j.ydbio.2011.05.669
M3 - Article
C2 - 21664348
AN - SCOPUS:79960561671
VL - 356
SP - 445
EP - 459
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -