更新于：2024-05-01
ISL1
ISL LIM homeobox 1
更新于：2024-05-01
基本信息
别名 Insulin gene enhancer protein ISL-1、ISL LIM homeobox 1、Isl-1 + [3] |
简介 DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1 (By similarity). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity). |
关联
100 项与 ISL1 相关的临床结果
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100 项与 ISL1 相关的转化医学
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2024-02-22Genetics
Sall genes regulate hindlimb initiation in mouse embryos.
Article
作者: Katherine Q Chen ; Hiroko Kawakami ; Aaron Anderson ; Dylan Corcoran ; Aditi Soni ; Ryuichi Nishinakamura ; Yasuhiko Kawakami
Vertebrate limbs start to develop as paired protrusions from the lateral plate mesoderm at specific locations of the body with forelimb buds developing anteriorly and hindlimb buds posteriorly. During the initiation process, limb progenitor cells maintain active proliferation to form protrusions and start to express Fgf10, which trigger molecular processes for outgrowth and patterning. Although both processes occur in both types of limbs, forelimbs (Tbx5) and hindlimbs (Isl1) utilize distinct transcriptional systems to trigger their development. Here, we report that Sall1 and Sall4, zinc finger transcription factor genes, regulate hindlimb initiation in mouse embryos. Compared to the 100% frequency loss of hindlimb buds in TCre; Isl1 conditional knockouts, Hoxb6Cre; Isl1 conditional knockout causes a hypomorphic phenotype with only approximately 5% of mutants lacking the hindlimb. Our previous study of SALL4 ChIP-seq showed SALL4 enrichment in an Isl1 enhancer, suggesting that SALL4 acts upstream of Isl1. Removing one allele Sall4 from the hypomorphic Hoxb6Cre; Isl1 mutant background caused loss of hindlimbs, but removing both alleles caused an even higher frequency of loss of hindlimbs, suggesting a genetic interaction between Sall4 and Isl1. Furthermore, TCre-mediated conditional double knockouts of Sall1 and Sall4 displayed a loss of expression of hindlimb progenitor markers (Isl1, Pitx1, Tbx4) and failed to develop hindlimbs, demonstrating functional redundancy between Sall1 and Sall4. Our data provides genetic evidence that Sall1 and Sall4 act as master regulators of hindlimb initiation.
2024-02-17General and comparative endocrinology
Mechanistic study of transcription factor Sox18 during heart development.
Article
作者: Jianxin Liang ; Imtiaz Ul Hassan ; Man Yee Cheung ; Lei Feng ; Yi-Jyun Lin ; Qi Long ; Chengdong Wang ; Yuyue Ding ; Ziqing Wang ; Yuan Zhang ; Yulong Li ; Donghao Guo ; Xiaofang Guo ; Thomas Chi Bun Wong ; Muhammad Kaleem Samma ; Zixin Rong ; Xufeng Qi ; Dongqing Cai ; Sai-Ming Ngai ; Hui Zhao
Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.
2024-01-24The Journal of neuroscience : the official journal of the Society for Neuroscience
ISL1 and POU4F1 directly interact to regulate the differentiation and survival of inner ear sensory neurons.
Article
作者: Mei Xu ; Shuchun Li ; Xiaoling Xie ; Luming Guo ; Dongliang Yu ; Jiaping Zhuo ; Jacey Lin ; Lotem Kol ; Lin Gan
The inner ear sensory neurons play a pivotal role in auditory processing and balance control. Though significant progresses have been made, the underlying mechanisms controlling the differentiation and survival of the inner ear sensory neurons remain largely unknown. During development, ISL1 and POU4F transcription factors are co-expressed and are required for terminal differentiation, pathfinding, axon outgrowth and survival of neurons in the central and peripheral nervous systems. However, little is understood about their functional relationship and regulatory mechanism in neural development. Here, we have knocked out Isl1 or Pou4f1 or both in mice of both sexes. In the absence of Isl1, the differentiation of cochleovestibular ganglion (CVG) neurons is disturbed and that Isl1-deficient CVG neurons display defects in migration and axon pathfinding. Compound deletion of Isl1 and Pou4f1 causes a delay in CVG differentiation and results in a more severe CVG defect with a loss of nearly all of spiral ganglion neurons (SGNs). Moreover, ISL1 and POU4F1 interact directly in developing CVG neurons and act cooperatively as well as independently in regulating the expression of unique sets of CVG-specific genes crucial for CVG development and survival by binding to the cis-regulatory elements including the promoters of Fgf10, Pou4f2 and Epha5 and enhancers of Eya1 and Ntng2 These findings demonstrate that Isl1 and Pou4f1 are indispensable for CVG development and maintenance by acting epistatically to regulate genes essential for CVG development.Significance Statement Inner ear neurons play critical roles in hearing and balance by transmitting auditory information in the form of electric signals from sensory hair cells to the brain. To study the genetic basis underlying their development, we identified the direct interaction and roles of transcription factors ISL1 and POU4F1 in regulating the development and maintenance of cochleovestibular ganglion (CVG) neurons. Moreover, our expression analysis uncovered that Isl1 and Pou4f1 are involved in the feedback regulation of CVG pioneer genes and control CVG differentiation genes. Furthermore, we identified and validated the function of the cis-regulatory elements bound by ISL1 and POU4F1 in vivo. Together, these findings provide insights into the gene regulatory network controlling the development of the inner ear neurons.
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