RESUMO
Embryonic hair follicle (HF) induction and formation is dependent on signalling crosstalk between the dermis and specialized dermal condensates on the mesenchymal side and epidermal cells and incipient placodes on the epithelial side, but the precise nature and succession of signals remain unclear. Platelet-derived growth factor (PDGF) signalling is involved in the development of several organs and the maintenance of adult tissues, including HF regeneration in the hair cycle. As both PDGF receptors, PDGFRα and PDGFRß, are expressed in embryonic dermis and dermal condensates, we explored in this study the role of PDGF signalling in HF induction and formation in the developing skin mesenchyme. We conditionally ablated both PDGF receptors with Tbx18(Cre) in early dermal condensates before follicle formation, and with Prx1-Cre broadly in the ventral dermis prior to HF induction. In both PDGFR double mutants, HF induction and formation ensued normally, and the pattern of HF formation and HF numbers were unaffected. These data demonstrate that mesenchymal PDGF signalling, either in the specialized niche or broadly in the dermis, is dispensable for HF induction and formation.
Assuntos
Derme/embriologia , Folículo Piloso/embriologia , Morfogênese/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Transdução de Sinais/fisiologia , Animais , Derme/citologia , Derme/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/fisiologia , Camundongos , Camundongos Mutantes , Modelos Animais , Morfogênese/genética , Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Transdução de Sinais/genéticaRESUMO
Mouse embryos acquire global DNA methylation of their genome during implantation. However the exact roles of DNA methyltransferases (DNMTs) in embryos have not been studied comprehensively. Here we systematically analyze the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos. We find a strict division of function between DNMT1, responsible for maintenance methylation, and DNMT3A/B, solely responsible for methylation acquisition in development. By analyzing severely hypomethylated embryos, we uncover multiple functions of DNA methylation that is used as a mechanism of repression for a panel of genes including not only imprinted and germline genes, but also lineage-committed genes and 2-cell genes. DNA methylation also suppresses multiple retrotransposons and illegitimate transcripts from cryptic promoters in transposons and gene bodies. Our work provides a thorough analysis of the roles of DNA methyltransferases and the importance of DNA methylation for transcriptome integrity in mammalian embryos.