Biology subjects

Maripuri, D. P.

Publications and source records attributed to Maripuri, D. P..

3 recordsLinked to original sources

bioRxiv2021

Wnt1-Cre mediated deletion of BMP7 suggests a role for neural crest-derived BMP7 in retina development and function

Neural crest (NC) contributes to various structures of the eye including cornea, ciliary body and retina. The association of NC-derived cells with hyaloid vessels in the form of pericytes is established. Similarly, persistence of NC-derived cells in the inner retina layer of the mature retina has been suggested. To date, no specific function has been attributed to them. NC-derived Bone morphogenetic protein 7 (BMP7) controls neurogenic properties in the brain and regulates glia differentiation. Here, we assessed the role of NC-derived BMP7 in the adult retina. BMP7 expression was determined using Bmp7LacZ reporter mice. BMP7 was expressed in GCL, IPL, OPL, and photoreceptors in P0, P14 and P30 retinas. Lineage tracing confirmed the presence of NC-derived cells in the GCL, INL, and ONL. Some but not all cells associated with vasculature. To test the function of NC-derived Bmp7, Bmp7fl/flWnt1cre (Bmp7ncko) mice were assessed by histological and functional methods. Loss of NC-derived cells in the GCL and INL and mild structural abnormalities were observed in the Bmp7ncko retina. Electroretinography revealed reduced a wave under photopic conditions and b wave under both scotopic and photopic conditions. The neuronal circuitry in the inner retina appeared affected, evidenced by decreased Calbindin in the GCL, IPL and INL. In the outer retina, S-opsin was increased. BMP7 expression in the mutant retina was strongly decreased at birth, but increased expression from cells other than NC was observed in the adult retina. This was associated with an increase in IBA1, suggestive that loss of NC-derived BMP7 predisposes to development of gliosis-like changes in the adult retina. Overall, our data reveal an important contribution of NC-derived BMP7 for the development and function of the inner and outer retina.

physiology↗

bioRxiv2021

iCOMIC: a graphical interface-driven bioinformatics pipeline for analyzing cancer omics data

Despite the tremendous increase in omics data generated by modern sequencing technologies, their analysis can be tricky and often requires substantial expertise in bioinformatics. To address this concern, we have developed a user-friendly pipeline to analyze (cancer) genomic data that takes in raw sequencing data (FASTQ format) as input and outputs insightful statistics on the nature of the data. Our iCOMIC toolkit pipeline can analyze whole-genome and transcriptome data and is embedded in the popular Snakemake workflow management system. iCOMIC is characterized by a user-friendly GUI that offers several advantages, including executing analyses with minimal steps, eliminating the need for complex command-line arguments. The toolkit features many independent core workflows for both whole genomic and transcriptomic data analysis. Even though all the necessary, well-established tools are integrated into the pipeline to enable out-of-the-box analysis, we provide the user with the means to replace modules or alter the pipeline as needed. Notably, we have integrated algorithms developed in-house for predicting driver and passenger mutations based on mutational context and tumor suppressor genes and oncogenes from somatic mutation data. We benchmarked our tool against Genome In A Bottle (GIAB) benchmark dataset (NA12878) and got the highest F1 score of 0.971 and 0.988 for indels and SNPs, respectively, using the BWA MEM - GATK HC DNA-Seq pipeline. Similarly, we achieved a correlation coefficient of r=0.85 using the HISAT2-StringTie-ballgown and STAR-StringTie-ballgown RNA-Seq pipelines on the human monocyte dataset (SRP082682). Overall, our tool enables easy analyses of omics datasets, with minimal steps, significantly ameliorating complex data analysis pipelines. Availability: https://github.com/RamanLab/iCOMIC

bioinformatics↗

bioRxiv2021

Loss of Foxc1 and Foxc2 function in chondroprogenitor cells disrupts endochondral ossification.

Endochondral ossification forms and grows the majority of the mammalian skeleton and is tightly controlled through gene regulatory networks. The forkhead box transcription factors Foxc1 and Foxc2 have been demonstrated to regulate aspects of osteoblast function in the formation of the skeleton but their roles in chondrocytes to control endochondral ossification are less clear. We demonstrate that Foxc1 expression is directly regulated by SOX9 activity, one of the earliest transcription factors to specify the chondrocyte lineages. Moreover we demonstrate that elevelated expression of Foxc1 promotes chondrocyte differentiation in mouse embryonic stem cells and loss of Foxc1 function inhibits chondrogenesis in vitro. Using chondrocyte-targeted deletion of Foxc1 and Foxc2 in mice, we reveal a role for these factors in chondrocyte differentiation in vivo. Loss of both Foxc1 and Foxc2 caused a general skeletal dysplasia predominantly affecting the vertebral column. The long bones of the limb were smaller and mineralization was reduced and organization of the growth plate was disrupted. In particular, the stacked columnar organization of the proliferative chondrocyte layer was reduced in size and cell proliferation in growth plate chondrocytes was reduced. Differential gene expression analysis indicated disrupted expression patterns in chondrogenesis and ossification genes throughout the entire process of endochondral ossification in Col2-cre;Foxc1{Delta}/{Delta};Foxc2{Delta}/{Delta} embryos. Our results suggest that Foxc1 and Foxc2 are required for correct chondrocyte differentiation and function. Loss of both genes results in disorganization of the growth plate, reduced chondrocyte proliferation and delays in chondrocyte hypertrophy that prevents correct ossification of the endochondral skeleton.

developmental biology↗