Mori Yusuke, Smith Sierra, Wang Jiacheng, Eliora Nadia, Heikes Kira L, Munjal Akankshi
Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Development. 2025 Jan 1;152(1). doi: 10.1242/dev.203003. Epub 2025 Jan 7.
During inner ear semicircular canal morphogenesis in zebrafish, patterned canal-genesis zones express genes for extracellular matrix component synthesis. These include hyaluronan and the hyaluronan-binding chondroitin sulfate proteoglycan Versican, which are abundant in the matrices of many developing organs. Charged hyaluronate polymers play a key role in canal morphogenesis through osmotic swelling. However, the developmental factor(s) that pattern the synthesis of the matrix components and regulation of hyaluronate density and swelling are unknown. Here, we identify the transcription factor Lmx1b as a positive transcriptional regulator of hyaluronan, Versican, and chondroitin synthesis genes crucial for canal morphogenesis. We show that Versican regulates hyaluronan density through its protein core, whereas the charged chondroitin side chains contribute to the hydration of hyaluronate-containing extracellular matrices. Versican-tuned properties of hyaluronate matrices may be a broadly used mechanism in morphogenesis with important implications for understanding diseases in which these matrices are impaired, and for hydrogel engineering for tissue regeneration.
在斑马鱼内耳半规管形态发生过程中，有规律的管生成区域表达细胞外基质成分合成相关基因。这些基因包括透明质酸以及与透明质酸结合的硫酸软骨素蛋白聚糖多功能蛋白聚糖，它们在许多发育器官的基质中含量丰富。带电荷的透明质酸盐聚合物通过渗透膨胀在半规管形态发生中起关键作用。然而，决定基质成分合成模式以及调节透明质酸盐密度和膨胀的发育因子尚不清楚。在此，我们确定转录因子Lmx1b是对半规管形态发生至关重要的透明质酸、多功能蛋白聚糖和软骨素合成基因的正向转录调节因子。我们发现多功能蛋白聚糖通过其蛋白核心调节透明质酸密度，而带电荷的硫酸软骨素侧链有助于含透明质酸的细胞外基质的水合作用。多功能蛋白聚糖调节的透明质酸基质特性可能是形态发生中广泛使用的一种机制，这对于理解这些基质受损的疾病以及组织再生的水凝胶工程具有重要意义。
