Abstract
Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down). GO enrichment analysis indicated that DEGs in both Brain and Lung were mainly enriched in biological processes ‘DNA-templated transcription and Transcription from RNA polymerase II promoter’, ‘multicellular organism development’, ‘cell differentiation’ and ‘apoptotic process’. In addition, COG classification showed that both were mostly involved in ‘Replication, Recombination, and Repair’, ‘Signal transduction and mechanism’, ‘Translation, Ribosomal structure and Biogenesis’ and ‘Transcription’. KEGG enrichment analysis showed that brain was mainly enriched in ‘Thyroid cancer’ pathway whereas lung in ‘Complement and Coagulation Cascades’ pathway. Transcription factor (TF) annotation analysis identified Zinc finger domain containing (ZF) proteins were mostly regulated in lung and brain. Interestingly, study identified genes Skor2, Gpr3711, Runx1, Erbb3, Frmd7, Fut10, Sox11, Hapln1, Tfap2c and Plxnb3 from brain that play important roles in neuronal cell maturation, differentiation, and survival; genes Hoxa5, Eya1, Errfi1, Sox11, Shh, Igf1, Ccbe1, Crh, Fgf9, Lama5, Pdgfra, Ptn, Rbp4 and Wnt7a from lung are important in lung development. Expression levels of the candidate genes were validated by qRT-PCR. Genome wide transcriptional analysis using wild type and Dip2a knockout mice in brain and lung at embryonic day 19.5 (E19.5) provided a genetic basis of molecular function of these genes.
Highlights
Disconnected interacting protein 2 homolog A (DIP2A) is a member of disconnected-interacting 2 (DIP2) protein family whose molecular anatomical function remains to be clarified
Dip2a was firstly identified in Drosophila as a novel transcription factor that interacts with disconnected gene needed for proper neural connection during visual system development in Drosophila [1,2,3]
Previous studies have shown that Dip2a is highly expressed in human brain and may play a role in axon patterning in Central Nervous System (CNS) [4]
Summary
DIP2A is a member of disconnected (disco)-interacting 2 (DIP2) protein family whose molecular anatomical function remains to be clarified. Dip2a has been previously identified as a risk gene associated with neurodevelopment diseases like autism spectrum disorder, development dyslexia and Alzheimer diseases [7,8,9]. All of these evidences strongly support the role of Dip2a gene in both vertebrate and invertebrate nervous system development. Which biological process or molecular function is regulated by Dip2a gene during embryonic brain development is not known
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