Multi-scale modulation of organ adaptation

Organs modulate their functions and forms to adapt to changing physiological needs and external stimuli. Current understanding of organogenesis revealed how molecules and cells work together to build an organ. The new scientific challenge is to understand how, at different life stages, an organ can maintain basic epigenetic memory and still be able to respond to new stimuli to reach optimal performance. We think such continuous interactions, or multi-scale modulation of organ adaptation, may exist in many organs using similar fundamental principles. To this end, the avian integument provides a unique opportunity to explore these principles because of its distinct patterns, regional specific morphology, quantitative control, and post- natal cyclic regeneration. Together, these attributes provide a highly complex plumage pattern that can change dynamically at different times and help birds successfully adapt to different environments. Thus, the avian integument presents a platform to analyze how stem cells and their environmentally modulatable niches interact to attain remarkably diverse, yet well-coordinated organ architectures. We will explore these novel principles in two projects. Project 1, Multi-scale organ morphogenesis. There is multi-dimensional regulation of organ size. To study the mechanistic control in depth, we will only focus on how feather length is regulated in this proposal. Whether this regulation is intrinsically or extrinsically controlled will be probed with stem cell behavior analyses including gene mis-expression and single-cell RNA analyses. We will compare feathers of different lengths in different body positions, different physiological ages and in different chicken variants. We will develop a model on how the feather length is regulated to achieve an almost mathematical relationship with its neighbors. Project 2, Environmental adaptation of organ phenotype. We will study how birds use molting / regenerative cycling to reset follicle niches and adult feather phenotypes through sex hormones and seasonal changes. To study mechanistic control in-depth, here we will focus on two experimental procedures (i) ovariectomizing female chickens, which converts sickle feathers to the male forms, and (ii) adding estradiol to male chickens, which convert sickle feathers to female forms. The epigenetic profiles of stem cells, niches and how they are altered by hormone status will be studied. This study will provide new knowledge on how an organ adjusts its homeostasis for the best possible adaptation during each organism’s lifetime.