Scl and Lyl1 Are Redundant in Erythropoiesis

Stem cell leukaemia (Scl) and Lymphoblastic lymphoma derived sequence 1 (Lyl1) are the only hematopoiesis-specific basic Helix-loop-helix (bHLH) transcription factors. During development, Lyl1 is unable to compensate for Scl; with death of Scl-null embryos at e9.5 due complete absence of primitive hematopoiesis and defective vascular development. In contrast, Lyl1 can compensate for Scl in adult hematopoietic stem cells. To further explore the role of these two bHLH factors during hematopoietic development, we deleted Scl with Cre recombinase under the control of the Epo receptor, which is active in late erythroid progenitors. Surprisingly, 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. In contrast EpoR-Cre Scl^D/D mice lacking Lyl1 died at e11.5-12.5 due to erythropoietic collapse (see figure 1). These experiments provide the first evidence for an important role of Lyl1 in erythroid development and suggest that death of Scl-null embryos is due to defects in endothelial development rather than lack of primitive erythropoiesis.

Figure 1.

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(A) Wildtype and (B) Scl/Lyl dko yolk sacs & embryos at e11.5.

Benzidine stains of (C) wildtype & (D) Scl/Lyl dko yolk sacs at e11.5.

Figure 1.

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(A) Wildtype and (B) Scl/Lyl dko yolk sacs & embryos at e11.5.

Benzidine stains of (C) wildtype & (D) Scl/Lyl dko yolk sacs at e11.5.

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