Either Scl or Lyl1 Is Required to Maintain Primitive Erythropoiesis

SCL (TAL1) and LYL1 are the predominant bHLH transcription factors expressed in erythropoiesis. Using a conditional allele of Scl, we have previously demonstrated redundancy of Scl in adult erythropoiesis. Similarly, adult erythropoiesis is maintained in Lyl1-deficient mice. To determine if these factors can compensate for each other, we deleted Scl with Cre recombinase under the control of the Epo receptor, which is active in late erythroid progenitors from embryonic day 8.5. Embryos lacking Scl in erythroid progenitors (EpoR-Cre Scl^D/D) were born at the expected Mendelian frequency with only a mild anemia in adult mice, indicating Scl was not required for primitive or definitive erythropoiesis. In contrast EpoR-Cre Scl^D/D mice lacking Lyl1 died at e11.5 due to erythropoietic collapse. Gene expression profiling of yolk sacs prior to the loss of erythrocytes (E9.5) revealed reduced Gata1, Fog1, Klf1 and the primitive b-globins. In contrast, expression of Gata2 and Runx1 were increased despite absence of Scl and Lyl1. Development of embryonic stem cells from these mice will determine if Gata1 is key downstream target of the Scl/Lyl1 complex for primitive erythropoiesis.