title: Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation.
abstract: CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using a morpholino-antisense-oligonucleotide-based zebrafish model for CHARGE syndrome, we uncover a complex spectrum of abnormalities in the neural crest and the crest-derived cell types. We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment cells in a CHARGE model. We also observe defects in the specification of peripheral neurons and the craniofacial skeleton as previously reported. Chd7 morphants have impaired migration of neural crest cells and deregulation of sox10 expression from the early stages. Knocking down Sox10 in the zebrafish CHARGE model rescued the defects in Schwann cells and craniofacial cartilage. Our zebrafish CHARGE model thus reveals important regulatory roles for Chd7 at multiple points of neural crest development viz., migration, fate choice and differentiation and we suggest that sox10 deregulation is an important driver of the neural crest-derived aspects of Chd7 dependent CHARGE syndrome.
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India and.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Asad
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Pandey
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India and.
authors.forename: Aswini
authors.initials: A
authors.lastname: Babu
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.|Center for Craniofacial Molecular Biology, Ostrow School of Dentistry and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kaivalya
authors.initials: K
authors.lastname: Shevade
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India and.
authors.forename: Shruti
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Ranjan
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India and.
authors.forename: Vinod
authors.initials: V
authors.lastname: Scaria
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bajpai
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, New Delhi, 110025, India chetana@igib.in chetana@igib.res.in.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India and.
authors.forename: Chetana
authors.initials: C
authors.lastname: Sachidanandan
mesh_terms: D000818:Animals; D058747:CHARGE Syndrome / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D060172:Morpholinos / Q000235:genetics; D009432:Neural Crest / Q000254:growth & development / Q000473:pathology; D010641:Phenotype; D055757:SOXE Transcription Factors / Q000235:genetics*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D060172:Morpholinos; D055757:SOXE Transcription Factors; D029961:Zebrafish Proteins; C442229:sox10 protein, zebrafish; D004265:DNA Helicases; C491434:CHD7 protein, human; C569452:Chd7 protein, zebrafish