**3. Hemoglobin expression during embryogenesis**

In vertebrates, there are typically several forms of Hb differing in composition of polypeptide chains and for oxygen transport under special conditions in various stages of human development. The developmental changes in Hb production are brought by differential activation of globin genes, which is largely determined at level of transcription. This process is known as hemoglobin switching [11].

During early stages of human development, embryonic Hb is expressed in RBC progenitors, which develops in the yolk sac. This Hb molecule consists of two hetero dimmers of epsilon (ε) and zeta (ζ)-globin chains [12]. The first switch in globin composition occurs as the site of erythropoiesis changes from the yolk sac to the fetal liver at 12 weeks post-conception period. Production of the embryonic form (Hb Portland-2 (ζ2β2), Hb Portland-1 (ζ2γ2), Hb Gower-1 (ζ2ɛ2), Hb Gower-2 (α2ɛ2) is downregulated, and it is replaced by fetal hemoglobin (HbF) containing α- and γ-globin chains (**Table 1**) [6, 13, 14] and by 17 weeks, only 1% of cells continue to express ζ-globin [15]. The second switch occurs approximately 6 weeks after birth: where the levels of fetal γ-globin decline and are replaced with adult hemoglobin (HbA). HbF makes up less than 1% of total hemoglobin in most individuals by 1 year of age [3]. The embryonic and adult α gene share 58% homology at amino acid level [16].
