Worldwide the demand for renewable energy made from non-food plant biomass is increasing. Plant biomass (or ‘lignocellulose’) found in plant cell walls serves as an attractive alternative to the current biomass feedstocks, i.e., corn and sugar cane. Cell walls of most plants are composed of energy-rich polysaccharide polymers that can be broken down (‘saccharification’) to produce many bio-based products (e.g., bioplastics, fibers for textile) and bioethanol. Previous studies have provided valuable information towards our understanding of cell wall biosynthesis, particularly of genes involved in this process. However, little is known about the cellular modifications associated with wall deposition and how these changes are regulated. The goal of this work is to address both the cellular and molecular mechanisms underlying secondary wall synthesis during sclerenchyma cell develpment using Brachypodium distachyon, a model for biomass feedstocks. To date we have begun to characterize sclerenchyma cell formation using a variety of molecular and 3D reconstruction tools, to gain a better understanding of the timing of secondary wall deposition. In addition, we are now focusing our attention to the molecular regulators (i.e., transcription factors or/and processing enzymes) of sclerenchyma cell differentiation and maturation by applying several physical and chemical approaches, including laser microdissection, transcriptomics, and cell wall composition analysis assays towards these goals. Ultimately, this work is improving our knowledge of secondary cell wall synthesis while identifying the regulators of this process to improve biomass saccharification. Conversely, this work addresses concerns for sustainable sources of energy, fibers, and chemicals by creating a dedicated biomass crop.