在哺乳动物半圆通道和耳发育过程中,CHD7和SOX2在一个共同的基因调节网络中起作用
Jingxia Gao1, Jennifer M Skidmore1, Jelka Cimerman1
1Department of Pediatrics, The University of Michigan, Ann Arbor, MI 48109.
概括
CHD7和SOX2的联合损失会损害内耳的发育,导致形并影响细胞增殖. 这些基因对于调节早期耳朵发育和基因表达至关重要.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
背景情况:
- 内耳的发育依赖于精确的表观遗传和转录控制.
- CHD7 (染色体螺旋酶DNA结合蛋白) 和SOX2 (与SRY相关的HMG盒子转录因子) 涉及听觉和前庭发育.
- 耳朵发育中的CHD7和SOX2之间的遗传相互作用在很大程度上仍未被探索.
研究的目的:
- 在内耳发育过程中调查Chd7和Sox2之间的遗传相互作用.
- 阐明CHD7和SOX2在调节发育的耳囊细胞的转录格局中的作用.
- 为了确定关键的发育时期和基底的分子机制CHD7-SOX2互动在耳朵.
主要方法:
- 对小鼠内耳发育的分析,小鼠服用不同剂量的Chd7和Sox2.2.
- 在表达Sox2的细胞中,有条件的,可诱导的Chd7损失.
- 在全基因组RNA测序和染色质标记 (CUT&Tag) 研究中.
主要成果:
- 结合Chd7和Sox2的哈普洛缺陷导致眼球细胞增殖减少,严重的半圆通道形,并缩短了带有异位毛细胞的带.
- 鉴定出了一个关键时期 (~E9.5) 对联合Chd7和Sox2损失的敏感性.
- 显示CHD7调节Sox2表达,并在控制关键ottic模式基因 (Pax2,Otx2) 的基因调节网络中早期起作用.
- CHD7和SOX2在转录起始部位和增强剂之间独立和合作结合,调节细胞原始细胞基因表达.
结论:
- 在早期内耳发育中,CHD7和SOX2起着重要的合作作用.
- 它们的相互作用对调节眼膜前代细胞基因表达和发育至关重要.
- 这些发现可能有助于对综合征和非综合征性听力或平衡障碍的理解和潜在的治疗策略.
相关概念视频
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
01:13The Cochlea
44.9K
The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.
44.9K
01:33Pleiotropy
40.4K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.4K
01:16Anatomy of the Ear
8.4K
Auditory sensation, commonly called hearing, involves the transformation of sonic waves into neural impulses facilitated by the structures of the auditory organ. The prominent, flesh-like structure on the side of the head, called the auricle, directs sound waves towards the auditory canal. The auricle is often mislabeled as the pinna, a term more aligned with mobile structures like a feline's external ear. The auditory canal penetrates the cranium via the external auditory meatus of the...
8.4K
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
01:22Hair Cells
40.4K
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
40.4K