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成对盒转录因子EGL-38将表皮生长因子受体(EGFR)信号传导与外阴中细胞类型特异性顶端细胞外基质的组装联系起来。

The Pax transcription factor EGL-38 links EGFR signaling to assembly of a cell-type specific apical extracellular matrix in the vulva.

作者信息

Schmidt Helen F, Darwin Chelsea B, Sundaram Meera V

机构信息

Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

出版信息

bioRxiv. 2024 Sep 6:2024.09.04.611291. doi: 10.1101/2024.09.04.611291.

Abstract

The surface of epithelial tissues is covered by an apical extracellular matrix (aECM). The aECMs of different tissues have distinct compositions to serve distinct functions, yet how a particular cell type assembles the proper aECM is not well understood. We used the cell-type specific matrix of the vulva to investigate the connection between cell identity and matrix assembly. The vulva is an epithelial tube composed of seven cell types descending from EGFR/Ras-dependent (1°) and Notch-dependent (2°) lineages. Vulva aECM contains multiple Zona Pellucida domain (ZP) proteins, which are a common component of aECMs across life. ZP proteins LET-653 and CUTL-18 assemble on 1° cell surfaces, while NOAH-1 assembles on a subset of 2° surfaces. All three ZP genes are broadly transcribed, indicating that cell-type specific ZP assembly must be determined by features of the destination cell surface. The paired box (Pax) transcription factor EGL-38 promotes assembly of 1° matrix and prevents inappropriate assembly of 2° matrix, suggesting that EGL-38 promotes expression of one or more ZP matrix organizers. Our results connect the known signaling pathways and various downstream effectors to EGL-38/Pax expression and the ZP matrix component of vulva cell fate execution. We propose that dedicated transcriptional networks may contribute to cell-appropriate assembly of aECM in many epithelial organs.

摘要

上皮组织的表面覆盖着顶端细胞外基质(aECM)。不同组织的aECM具有不同的组成以发挥不同的功能,然而特定细胞类型如何组装合适的aECM尚不清楚。我们利用外阴的细胞类型特异性基质来研究细胞身份与基质组装之间的联系。外阴是一个上皮管,由源自表皮生长因子受体/原癌基因Ras依赖性(1°)和Notch依赖性(2°)谱系的七种细胞类型组成。外阴aECM包含多种透明带结构域(ZP)蛋白,这些蛋白是生物界aECM的常见组成成分。ZP蛋白LET-653和CUTL-18在1°细胞表面组装,而NOAH-1在一部分2°细胞表面组装。所有这三个ZP基因都广泛转录,这表明细胞类型特异性的ZP组装必定由目标细胞表面的特征决定。配对盒(Pax)转录因子EGL-38促进1°基质的组装并防止2°基质的不适当组装,这表明EGL-38促进一种或多种ZP基质组织者的表达。我们的研究结果将已知的信号通路和各种下游效应物与EGL-38/Pax表达以及外阴细胞命运执行的ZP基质成分联系起来。我们提出,专门的转录网络可能有助于许多上皮器官中aECM的细胞特异性组装。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a49/11398461/c4c09dc8b742/nihpp-2024.09.04.611291v1-f0001.jpg

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