Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver

Abstract

The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size.

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Figure 1: Pancreatic progenitor cell ablation.
Figure 2: Lack of compensatory growth during pancreas development.
Figure 3: Small pancreata do not exhibit catch-up growth.
Figure 4: Pdx1 -deficient blastocyst complementation.
Figure 5: Size variation after pancreas complementation.
Figure 6: Compensatory growth during liver development.

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Acknowledgements

We thank R. MacDonald, R. DePinho, G. Fishman, H. Bujard and C. Wright for sharing mouse strains, C. Wright for sharing antibodies, and A. Nagy for providing ES cells. We also thank M. Stolovich-Rein and Y. Dor for assistance in quantifying chimaerism, A. Greenwood for assistance with pancreatic lineage quantification, and A. Panikkar for assistance with morphometric analysis. We are grateful to J. Rajagopal, D. Huangfu, Y. Dor and Q. Zhou for critically reading the manuscript, and to S. Snapper, K. Eggan and H. Akutsu for suggestions and technical expertise. L. Peeples and J. Zhang provided assistance with the statistical analysis. B.Z.S. is supported by an award from NIDDK. D.A.M. is an investigator of the Howard Hughes Medical Institute.

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Correspondence to Ben Z. Stanger or Douglas A. Melton.

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This file contains Supplementary Methods, Supplementary Figures 1-7 with Legends, Supplementary Table 1 and additional references. (PDF 1650 kb)

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Stanger, B., Tanaka, A. & Melton, D. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445, 886–891 (2007). https://doi.org/10.1038/nature05537

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