ABSTRACT
Within the hair follicle (HF) niche, dermal papilla (DP) cells are well known for the hair induction capacity; however, DP cell signaling also regulates HF pigmentation. Here we describe how Sox2 in the DP is a key regulator of melanocyte signaling. To study the largely unknown regulatory role the DP has on hair pigmentation, we characterize leptin receptor (Lepr) expression in the skin and as a genetic tool to target the DP. Sox2 ablation in the DP results in a phenotypic switch from eumelanin to pheomelanin. Mechanistically, we describe a temporal upregulation of Agouti and downregulation of Corin, directly by Sox2 in the DP. We also show that bone morphogenic protein (BMP) signaling regulation by Sox2 is responsible for downregulating MC1R, Dct, and Tyr in melanocytes of Sox2 cKO mice. Thus, we demonstrate that Sox2 in the DP regulates not only the choice of hair pigment but also the overall HF pigment production.
Subject(s)
Hair Follicle , Hair , Animals , Hair Follicle/metabolism , Mice , Pigmentation , Signal Transduction/physiology , Skin/metabolismABSTRACT
Members of the PR/SET domain-containing (PRDM) family of zinc finger transcriptional regulators play diverse developmental roles. PRDM10 is a yet uncharacterized family member, and its function in vivo is unknown. Here, we report an essential requirement for PRDM10 in pre-implantation embryos and embryonic stem cells (mESCs), where loss of PRDM10 results in severe cell growth inhibition. Detailed genomic and biochemical analyses reveal that PRDM10 functions as a sequence-specific transcription factor. We identify Eif3b, which encodes a core component of the eukaryotic translation initiation factor 3 (eIF3) complex, as a key downstream target, and demonstrate that growth inhibition in PRDM10-deficient mESCs is in part mediated through EIF3B-dependent effects on global translation. Our work elucidates the molecular function of PRDM10 in maintaining global translation, establishes its essential role in early embryonic development and mESC homeostasis, and offers insights into the functional repertoire of PRDMs as well as the transcriptional mechanisms regulating translation.
Subject(s)
Gene Expression Regulation, Developmental , Mice/metabolism , Transcription Factors/metabolism , Animals , Embryonic Development , Embryonic Stem Cells/metabolism , Eukaryotic Initiation Factors/genetics , Eukaryotic Initiation Factors/metabolism , Female , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Male , Mice/embryology , Mice/genetics , Protein Biosynthesis , Transcription Factors/geneticsABSTRACT
Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species.
