Mizuho Mimoto

Cell & Developmental Biology

Mizuho Mimoto, Gokhan Dalgin, Devorah Goldman, Jan Christian

The Role of xGATA-2 and xFOG in Regulating Primitive Erythropoieis

Primitive hematopoiesis in the vertebrate embryo is regulated in a non

cell-autonomous fashion.  Specifically, in Xenopus [italics] embryos,

signals derived from the ectoderm are required for the commitment of

ventral mesoderm to an erythroid fate.  We have recently demonstrated

that the transcription factor, GATA-2 [italics], is required in

ectodermal cells to induce differentiation of ventral mesoderm into

mature erythrocytes.  It has also been shown that an interacting

co-factor, Friend of GATA (FOG) [italics], can both positively and

negatively regulate GATA [italics] target genes in a context-specific

manner.  Over-expression of FOG [italics] in this system results in a

loss of blood.  Though it is well-established that GATA-2 [italics]

plays a key role in early red blood cell formation, the specific

effector genes by which it controls this process have yet to be

determined.  In addition, the role FOG [italics] that plays in

regulating GATA-2 [italics] during primitive blood development remains

unresolved.  We hypothesize that interactions between FOG [italics]

and GATA-2 [italics] in the ectoderm are required for the expression

of target genes that are essential for erythropoiesis in the ventral

mesoderm.  In support of this model, we have shown that FOG [italics]

and GATA-2 [italics] are co-expressed in the ectoderm throughout early

Xenopus development.  To further test this hypothesis, we will inject

FOG [italics] morpholinos into Xenopus embryos to investigate whether

FOG-GATA-2 [italics] interaction is required in the ectoderm to induce

red blood cell formation.  In addition, we will use microarray

analysis to identify transcriptional targets of xGATA-2 [italics]

expressed in the ectoderm at the appropriate time in development, to

render ventral mesoderm competent to form primitive red blood cells.

Molecular interactions involved in regulating primitive hematopoiesis

are conserved in vertebrates and have been shown in many cases to be

analogous to those involved in promoting definitive hematopoiesis in

adults.  Understanding how these pathways are regulated in a

physiologic context will contribute both to a greater understanding of

normal hematopoiesis as well as offer insight into novel therapeutic

targets for the treatment or prevention of adult blood-related

diseases such as anemia and leukemia.