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iScience 2023 Sep 15;269:107665. doi: 10.1016/j.isci.2023.107665.
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Time-resolved quantitative proteomic analysis of the developing Xenopus otic vesicle reveals putative congenital hearing loss candidates.

Baxi AB , Nemes P , Moody SA .

Over 200 genes are known to underlie human congenital hearing loss (CHL). Although transcriptomic approaches have identified candidate regulators of otic development, little is known about the abundance of their protein products. We used a multiplexed quantitative mass spectrometry-based proteomic approach to determine protein abundances over key stages of Xenopus otic morphogenesis to reveal a dynamic expression of cytoskeletal, integrin signaling, and extracellular matrix proteins. We correlated these dynamically expressed proteins to previously published lists of putative downstream targets of human syndromic hearing loss genes: SIX1 (BOR syndrome), CHD7 (CHARGE syndrome), and SOX10 (Waardenburg syndrome). We identified transforming growth factor beta-induced (Tgfbi), an extracellular integrin-interacting protein, as a putative target of Six1 that is required for normal otic vesicle formation. Our findings demonstrate the application of this Xenopus dataset to understanding the dynamic regulation of proteins during otic development and to discovery of additional candidates for human CHL.

PubMed ID: 37670778
PMC ID: PMC10475516
Article link: iScience
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acan acta1 actb actg1 ak2 anxa1 anxa2 anxa3 anxa4 bax bcap31 casp3 chd1 chd7 col11a1 col11a2 col11a2l col12a1 col1a1 col1a2 col2a1 col3a1 col4a6 col9a2 col9a3 crym dlx5 dmd dynll1 eef2.1 eif3b eif5a etf1 farsb fas fbn2 fn1 foxc2 gapdh gng5 hapln1 hdac3 kars1 lars2 ldb3 lrp2 lum map2 mapk1 mfap2 mtap myh3 myh9 myo1c myo6 myoz1 npm1 otog otor pa2g4 pax2 plod3 prpf3 pxn rpl7 rpl9 rplp1 rplp2 rps19 rps20 sars2 serpina6 sfrp1 six1 snrpa sox10 tecta tgfb1 tgfbi timm10 timm8a timm9 tnc tpm1
GO keywords: integrin-mediated signaling pathway [+]
Antibodies: Digoxigenin Ab2
Morpholinos: tgfbi MO3 tgfbi MO4

Disease Ontology terms: CHARGE syndrome [+]
Phenotypes: Xla Wt + tgfbi MO (Fig. 7 C r1c2, r2c2; D E)

Article Images: [+] show captions
References [+] :
Ahmed, The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel. 2007, Pubmed