In this issue of Blood, Cheng and colleagues report first on intriguingly complex pre–messenger RNA (pre-mRNA) global alternate splicing (AS) events that occur in primary erythroblasts. Predominant regulatory roles then are implicated for a Muscleblind-like (MBNL) splicing factor, Mbnl1 (an AS regulator in pluripotent embryonic stem [ES] cells and myoblasts), and for nuclear distribution element like-1 (Ndel1) as a Mbnl1 target. Via loss-of-function (LOF) analyses, Mbnl1 and Ndel1 further are evidenced to support erythroblast development.
