SoxD and SoxF in hematopoietic and vascular development.

Members of the Sry-related HMG box (SOX) family of transcription factors are found throughout the animal kingdom and play widespread roles during development. SoxF proteins are expressed in endothelial cells during mouse vascular development and they are involved in the regulation of different aspect in vascular development. In the last year, the key role of Sox18 during early lymphatic specification has been well elucidated in mouse. We decided to investigate specifically the role played by sox18 in zebrafish lymphatic development and the interplay between sox18 and the central lymphatic growth factor vegfc. The external development, the optical clarity and the capacity to easily visualize the vascular tree and the blood circulation using a variety of labelling techniques make the zebrafish a useful model to study vascular morphogenesis in vivo. Since the initial description of the zebrafish lymphatic system in 2006 it has emerged as a very potent system to study lymphangiogenesis too. The presented data show that the role of Sox18 in lymphangiogenesis is evolutionarily conserved in zebrafish and suggest an unappreciated crosstalk between Sox18 and one of the most potent lymphangiogenic growth factors. SoxD proteins are an atypical SOX group because they lack a transrepression or a transactivation domain, however they participate in transcriptional activation and repression in different contexts. Sox13 has been described to interact with Tcf1 in T cells, thereby preventing it from binding to target genes, and influencing T-cell differentiation. In literature, we found some hints that suggested a possible involvement for Sox13 in vascular development. We identified the zebrafish SOX13 ortholog and, due to our interest in the role of SOX genes in vascular development, we decided to verify its potential activity. Zebrafish sox13 is expressed in the II central nervous system, transiently in the developing vasculature and in primitive erythropoietic tissue. We observed that its knockdown impairs angiogenesis in different vascular beds and intersomitic vessels defects are apparently linked to an improper Notch signalling activation. We discovered also an unproposed role for Sox13 in primitive erythropoieis. We observed that sox13 knockdown affects primitive erythrocyte maturation. Altogether, the data collected during my PhD period contributed to the enrichment of the complex network that engages SOX proteins during embryo development.