During embryonic development, gastrulation leads to the specification of mesoderm that will contribute to the cardiovascular system, the muscles, and many other tissues. In zebrafish, mesoderm appears at 6 hours post fertilization (hpf), and the first blood progenitors can be detected as early as 12hpf in the lateral plate mesoderm (LPM). To better understand the mechanisms involved in LPM patterning into blood, we performed transcriptome analysis to compare the first erythrocyte progenitors with the first angioblasts, sorted at 12hpf. We identified a new gene, bif (BMP-inhibitory factor) that is specifically expressed in the posterior LPM that will give rise to primitive red blood cells. bif is expressed as early as 11hpf in the LPM and then remains specifically expressed in erythrocytes. bif is a transcription factor of unknown function. Gain-of-function experiments resulted in an expansion of the blood marker gata1 in the posterior LPM at 12hpf, in a similar way that was observed when BMP signalling is perturbed. Moreover, overexpression of bif resulted in the duplication of the tail axis at 24hpf, and the mis-expression of cloaca markers, two phenotypes also observed in BMP-impaired embryos. Further analyses by qPCR and in situ hybridization showed that bif expression diminishes the expression of BMP target genes.
We thus conclude that bif, specifies the LPM towards blood fate by down-regulating BMP signalling. We are now building new transgenic tools, as well as mutants, in order to understand the full spectrum of bif actions.