Role of skeletal muscle in the shaping of organs and cell fate choices

As a developmental biologist, I study the role of muscle in the shaping of organs and cell fate choices during embryonic development. This is a unique research program that deals with a very fundamental biological question of the developmental relationship between the genotype and the phenotype. This program is entirely based on employing mouse mutants and performing anatomical (or macroscopic), histological (or microscopic) and ultra-structural (with transmission electron microscope) analysis of the tissues of interest. The uniqueness of my approach is in our ability to genetically excise an entire tissue type and obtain a mouse embryo and fetus viable only while in the womb and without any skeletal (or striated) muscle. This compound mutant (designated as Myf5-/-:MyoD-/-, because of the absence of two primary myogenic regulatory factors) provides me with the opportunity to study the development of organs (e.g., the lung) and cells (e.g., motor neurons) in the complete absence of mechanical and endocrine contributions from the muscle, respectively. In other words, we study lung development in the absence of fetal breathing-like movements, and we study the survival of motor neurons in the absence of target-provided neurotrophic support. Importantly, these two examples have been providing the field of developmental biology with new knowledge on the role of mechanical cues from the muscle in organogenesis and on the role of muscle in providing the neurotrophic support to the motor neurons for their survival and maintenance. More immediate benefits of our research are in: attributing a new function to a series of genes of interest, generating mouse models of human diseases or of biological phenomena, revealing new molecular markers for research (and potentially for a disease).