**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MORTALITY, WEANING STRESS, AND HEALTH CHALLENGES IN YOUNG PIGS REMAIN A SIGNIFICANT CONCERN IN THE SWINE INDUSTRY, AS THEY REDUCE GROWTH, FEED EFFICIENCY, AND PROFITABILITY. THE SMALL INTESTINE IS CRITICAL TO THIS, AS GROWTH RELIES ON THE PIG'S ABILITY TO EFFICIENTLY DIGEST AND ABSORB NUTRIENTS ACROSS THE SMALL INTESTINAL EPITHELIUM WHILE REMAINING IMPENETRABLE TO PATHOGENS. EFFICIENCY OF SMALL INTESTINAL DIGESTIVE AND ABSORPTIVE FUNCTION DEPENDS ON THE TYPES OF CELLS PRESENT, ACTIVITY OF THESE CELLS, RATE OF CELL TURNOVER, AND INTESTINAL SURFACE AREA. ALTHOUGH IT HAS BEEN ESTABLISHED THAT THE SMALL INTESTINE UNDERGOES MAJOR DEVELOPMENTAL AND FUNCTIONAL CHANGES IN THE FIRST 28 DAYS OF LIFE AND DURING STRESS EVENTS, HOW EPITHELIAL CELL TYPES CHANGE DURING THESE EVENTS AND THE MOLECULAR MECHANISMS UNDERLYING THESE CHANGES REMAINS UNCLEAR. IN ORDER TO DEVELOP TARGETED STRATEGIES TO IMPROVE PIG GROWTH, WE MUST FIRST UNDERSTAND THE SIGNALING PATHWAYS UNDERLYING INTESTINAL DEVELOPMENT AND CELLULAR COMPOSITION. WE HYPOTHESIZE THAT TWO SIGNALING PATHWAYS (NOTCH AND WNT) ARE CRITICAL REGULATORS OF INTESTINAL DEVELOPMENT AND DIGESTIVE FUNCTION. DIET TRANSITIONS AND STRESS EVENTS (SUCH AS WEANING OR PATHOGEN CHALLENGE) ALTER SMALL INTESTINAL CELLULAR COMPOSITION THROUGH THESE SIGNALING PATHWAYS. THIS IMPACTS EFFICIENCY OF NUTRIENT DIGESTION AND ABSORPTION, COMPROMISING GROWTH AND FEED EFFICIENCY. WE AIM TO TEST THIS HYPOTHESIS BY CHARACTERIZING THE MOLECULAR MECHANISMS UNDERLYING INTESTINAL CELL COMPOSITION AND DEVELOPMENT IN EARLY LIFE PIGS, AND HOW THESE PATHWAYS ARE MODULATED DURING AN INTESTINAL HEALTH CHALLENGE. WE EXPECT TO FIND THAT NOTCH AND WNT SIGNALING UNDERLIE THE DEVELOPMENTAL CHANGES THAT OCCUR IN THE INTESTINE OF EARLY LIFE PIGS DURING DIET TRANSITIONS AND WEANING STRESS. ADDITIONALLY, WE EXPECT TO FIND NOTCH AND WNT DYSREGULATION COINCIDE WITH LOSSES IN GROWTH AND FEED EFFICIENCY DURING HEALTH CHALLENGE. OVERALL, FINDINGS FROM THIS WORK WILL INCREASE OUR UNDERSTANDING OF THE MOLECULAR MECHANISMS THAT CONTROL SMALL INTESTINAL FUNCTION, AND WILL ALLOW US TO DEVELOP STRATEGIES TO IMPROVE NUTRIENT UTILIZATION IN PIGS. THIS WILL REDUCE MORTALITY, WEANING STRESS, DISEASE PRESSURE, PRODUCTION COSTS, AND RESOURCE UTILIZATION, RESULTING IN OVERALL IMPROVED PROFITABILITY AND SUSTAINABILITY OF THE SWINE INDUSTRY.