ORIGINAL PAPER Gene expression in bovine rumen epithelium during weaning identifies molecular regulators of rumen development and growth Erin E. Connor & Ransom L. Baldwin VI & Cong-jun Li & Robert W. Li & Hoyoung Chung Received: 29 August 2012 / Revised: 18 December 2012 / Accepted: 26 December 2012 / Published online: 13 January 2013 # Springer-Verlag Berlin Heidelberg (outside the USA) 2013 Abstract During weaning, epithelial cell function in the ru- men transitions in response to conversion from a pre-ruminant to a true ruminant environment to ensure efficient nutrient absorption and metabolism. To identify gene networks affected by weaning in bovine rumen, Holstein bull calves were fed commercial milk replacer only (MRO) until 42 days of age, then were provided diets of either milk + orchardgrass hay (MH) or milk + grain-based calf starter (MG). Rumen epithelial RNA was extracted from calves sacrificed at four time points: day 14 (n =3) and day 42 (n =3) of age while fed the MRO diet and day 56 (n =3/diet) and day 70 (n =3/diet) while fed the MH and MG diets for transcript profiling by microarray hybridiza- tion. Five two-group comparisons were made using Permutation Analysis of Differential Expression® to identify differentially expressed genes over time and developmental stage between days 14 and 42 within the MRO diet, between day 42 on the MRO diet and day 56 on the MG or MH diets, and between the MG and MH diets at days 56 and 70. Ingenuity Pathway Analysis (IPA) of differentially expressed genes during weaning indicated the top 5 gene networks in- volving molecules participating in lipid metabolism, cell mor- phology and death, cellular growth and proliferation, molecular transport, and the cell cycle. Putative genes functioning in the establishment of the rumen microbial population and associated rumen epithelial inflammation during weaning were identified. Activation of transcription factor PPAR-α was identified by IPA software as an important regulator of molecular changes in rumen epithelium that function in papillary development and fatty acid oxidation during the transition from pre-rumination to rumination. Thus, molecular markers of rumen development and gene networks regulating differentiation and growth of rumen epithelium were identified for selecting targets and methods for improving and assessing rumen development and function, particularly in the growing calf. Keywords Cattle . Growth . Microarray . Rumen . Weaning Introduction The rumen is a critical organ mediating nutrient uptake and use in cattle. In calves, efficient nutrient delivery, absorption, and metabolism depend upon the transition of the rumen during weaning from a pre-ruminant to a ruminant state. In the mature animal, the rumen epithelium is also responsible for several physiologically important functions, including absorption, transport, volatile fatty acid (VFA) metabolism, and protection. Unlike many organs, which comprise a smaller proportion of empty body weight (EBW) as the animal matures, the rumen increases from 30 to 70 % of the capacity of the gut during weaning (Warner et al. 1956) and increases as a percentage of EBW throughout lactation (Baldwin et al. 2004). Moreover, given the high metabolic activity of intestinal tissues in gener- al, the rumen epithelium is central to net efficiency of feed conversion in cattle during multiple stages of production. In order to create nutritional management strategies that improve nutrient use efficiency in cattle, knowledge and under- standing of regulatory control points governing differentiation, Electronic supplementary material The online version of this article (doi:10.1007/s10142-012-0308-x) contains supplementary material, which is available to authorized users. E. E. Connor (*) : R. L. Baldwin VI : C.-j. Li : R. W. Li Bovine Functional Genomics Laboratory, Agricultural Research Service, USDA, 10300 Baltimore Avenue, Bldg. 306, BARC-East, Beltsville, MD 20705, USA e-mail: erin.connor@ars.usda.gov H. Chung Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Suwon 441-701, South Korea Funct Integr Genomics (2013) 13:133–142 DOI 10.1007/s10142-012-0308-x