Abstract
BackgroundMajor changes in gene expression occur in the fetal brain to modulate the function of this organ postnatally. Thus, factors can alter the genomics of the fetal brain, predisposing to neurological disorders later in life. We hypothesized that the physiological dynamics of the immune system transcriptome of the fetal brain during the last stage of gestation will reveal patterns of immune function and development in the developing brain. In this study we applied weighted gene co-expression analysis of microarrays performed on ovine fetal brain samples, to model the changes in gene expression throughout the second half of gestation.ResultsClusters of co-expressed genes that strongly increase in expression toward the first day of extra-uterine life are related to the hematopoietic lineage, while activation of immune pathways is induced after birth. Moreover, the pattern of gene expression suggests induction of tolerance mechanisms, probably necessary to protect highly produced proteins –such as myelin basic protein- from an autoimmune attack.ConclusionsThis study provides insight into the dramatic changes in gene expression that take place in the brain during the fetal life, especially during the last stage of gestation, and suggests that the immune system may have an important role in maturation of the fetal brain, which if disrupted or altered, could have negative consequences in postnatal life.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1001) contains supplementary material, which is available to authorized users.
Highlights
Major changes in gene expression occur in the fetal brain to modulate the function of this organ postnatally
Enrichment and network analysis Significantly enriched Biological Processes (BP; p < 0.01; WebGestalt software [8]) of the positively correlated top modules from each brain region are shown in Additional file 6: Table S2
In agreement with other studies [1,9], groups of co-expressed genes that increase in expression toward the end of gestation are related with response to stress and stimulus, myelination, apoptosis, generation of energy, and angiogenesis, while genes that decrease in expression are mainly related to cell cycle
Summary
Major changes in gene expression occur in the fetal brain to modulate the function of this organ postnatally. Factors can alter the genomics of the fetal brain, predisposing to neurological disorders later in life. Normal brain development requires temporal changes in gene expression. The major changes in spatio-temporal gene expression occur during the late gestation fetal life [1]. Little is known about development of immune function in the fetal brain, there is a growing literature that some chronic diseases of the adult, such as hypertension [2], schizophrenia [3], and autoimmune disorders [4] are at least in part the result of immune dysfunction within the brain. The focus of studies on immune development in late development could provide a better understanding of mechanisms underpinning postnatal neurological disorders
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
