Proliferation Following Tetraploidization Regulates the Size and Number of Erythrocytes in the Blood Flow During Medaka Development, as Revealed by the Abnormal Karyotype of Erythrocytes in the Medaka TFDP1 Mutant

Background: For the delivery of oxygen, the correct size/number of erythrocytes is required for proper blood flow. Results: By combined analyses of wild-type (WT) medaka and the kyoho (kyo) mutant, we found proliferation-mediated adaptation for size/number of erythrocytes in the blood flow during medaka development. Before the start of heart beating in the WT medaka, the karyotype of erythrocytes was 2N-4N. After the start of blood flow, the karyotype changed to 4N-8N with tetraploidization, and the cell size became larger. After the start of intersegmental and pharyngeal blood flow, the erythrocytes became smaller. The medaka mutant kyo showed erythrocytes of large size, and positional cloning of kyo demonstrated the candidate gene TFDP1, indicating higher polyploidization due to arrest in S-phase in erythrocytes of the kyo mutant. Conclusions: From our findings, we uncovered a previously unrecognized system for the regulation of the size/number in the blood flow:proliferation of erythrocytes following tetraploidization during embryonic development. Developmental Dynamics 244:651-668, 2015. (c) 2015 Wiley Periodicals, Inc.