Sorghum is a crop widely cultivated in southern countries (Africa, Latin America, India) for human and animal consumption. It is also grown in northern countries for animal consumption and increasingly used for energy and biomaterials. These uses often rely on vegetative biomass valorization. Most of this biomass accumulates in secondary cell wall (SCW) of the stems as celluloses and xylans, which are tightly linked to lignins. Being able to monitor precisely the composition of SCW in sorghum can provide a major leverage to optimize its different uses. Understanding how SCW is deposited and regulated would allow breeding programs to develop varieties fitting the expectations of the different value chains. The identification of genes involved in SCW development in sorghum will contribute to improve our ability to optimize its composition and structure. Transcription factors (TF) are key targets because they are often responsible for fine-tuning biological processes. Moreover, they allow deciphering the downstream network. MYB and NAC TF families are already known to be involved in SCW regulation in other model species, but their roles still need to be addressed in sorghum. For this study, we carried out comparative genomics and co-expression network analysis to highlight NAC and MYB genes that are most likely to be involved in SCW regulation in sorghum. Based on these candidates, functional validation experiments are on-going. Firstly, the comparative genomics analysis identified 96 NAC and 170 MYB genes in sorghum. 34 NAC and MYB genes were recognized as orthologs of master regulators of SCW in other species. Moreover, phylogenetic dissimilarities within both families between monocotyledons and dicotyledons pointed out potential differences in SCW regulation between these two groups of angiosperms. Secondly, using transcriptomic data from developing sorghum internodes, we built co- expression networks. Using orthologs of previously identified TF as baits, we were ab