What makes a mammal special? Fur and hair, lactation, four-chambered hearts… During the 2018 Jenkinson Memorial Lecture, Prof. Elizabeth Robertson presented some of her lab’s findings on Blimp1/Prdm1 (referred to as Blimp1) protein function and its high relevance to development of key characteristics that define a mammal.
Blimp1 is a transcriptional repressor that recruits proteins which regulate the chromatin landscape and alter expression of certain genes. It is a member of the PRDM gene family, and like the other members of this gene family, Blimp1 has a number of regulatory functions ranging from B-lymphocyte maturation to gene expression in keratinocytes. Prof. Robertson’s group focused on the function of Blimp1 in the developing mouse embryo – what caused loss of function mutants to die at mid-gestation? Through investigating these mutant embryos, Prof. Robertson’s group discovered that these mutants exhibited placental deficiencies. They showed that Blimp1 was key in forming specialized cell populations in the developing placenta, and when Blimp1 expressing cells were not there, the placenta could not be formed properly and the fetus soon died due to lack of nutrients channeled through the placenta.
In addition, members of Prof. Robertson’s group noticed that Blimp1 was also highly expressed in the embryo’s developing gut tube, but 10 days after birth, Blimp1 expression was undetectable in gut lining. What was Blimp1 doing in the pre-natal gut, and how did this change in Blimp1 expression affect gut function? Investigation into mice with no Blimp1 expression in their gut tissue showed that these mutants did not exhibit abnormalities in gut development, but were smaller in size and most could not live past 10 days of birth. Although gut structure development was not compromised in these mutant mice, their pre-natal and post-natal gut gene expression profile closely resembled that of an adult mouse. This meant that their gut tissue was expressing enzymes required for breaking down adult food while they were in a life stage where they solely consumed milk, causing them to have difficulties in absorbing nutrients from milk.
Finally, Prof. Robertson showed that Blimp1 also had key functions in mammary gland development. Her group used cell-lineage tracing techniques to show that although Blimp1 expressing cells only made up <1% of the mammary gland lumen cell layer, they were crucial cells that produced daughter cells which contributed to mammary gland morphogenesis in puberty. Blimp1 identified long-lived unipotent stem cells that contributed greatly to mammary gland function and alveoli development during and pregnancy.
In short, Prof. Robertson showed that Blimp1 is a key protein involved in multiple pathways and has many functions, including placenta development, pre-natal to adult gut tissue transition, and mammary gland development. These functions are closely related to mammal gestation and lactation, which makes Blimp1 extremely important for early mammalian development. What is even more interesting is that Blimp1 is also found in non-mammals, including the chicken and zebrafish, but is expressed in a different spatial and temporal pattern. What exactly is Blimp1 doing in non-mammals? In addition, what are the factors controlling Blimp1 expression in the early mammal embryo? What are the enhancers and regulatory proteins involved in this process? There are still more questions to be answered about this key regulatory protein!
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Yichen Dai (Serena), DPhil student in the Holland group.
