scholarly journals Barhl1 Regulatory Sequences Required for Cell-Specific Gene Expression and Autoregulation in the Inner Ear and Central Nervous System

2008 ◽  
Vol 28 (6) ◽  
pp. 1905-1914 ◽  
Author(s):  
Ramesh Chellappa ◽  
Shengguo Li ◽  
Sarah Pauley ◽  
Israt Jahan ◽  
Kangxin Jin ◽  
...  

ABSTRACT The development of the nervous system requires the concerted actions of multiple transcription factors, yet the molecular events leading to their expression remain poorly understood. Barhl1, a mammalian homeodomain transcription factor of the BarH class, is expressed by developing inner ear hair cells, cerebellar granule cells, precerebellar neurons, and collicular neurons. Targeted gene inactivation has demonstrated a crucial role for Barhl1 in the survival and/or migration of these sensory cells and neurons. Here we report the regulatory sequences of Barhl1 necessary for directing its proper spatiotemporal expression pattern in the inner ear and central nervous system (CNS). Using a transgenic approach, we have found that high-level and cell-specific expression of Barhl1 within the inner ear and CNS depends on both its 5′ promoter and 3′ enhancer sequences. Further transcriptional, binding, and mutational analyses of the 5′ promoter have identified two homeoprotein binding motifs that can be occupied and activated by Barhl1. Moreover, proper Barhl1 expression in inner ear hair cells and cerebellar and precerebellar neurons requires the presence of Atoh1. Together, these data delineate useful Barhl1 regulatory sequences that direct strong and specific gene expression to inner ear hair cells and CNS sensory neurons, establish a role for autoregulation in the maintenance of Barhl1 expression, and identify Atoh1 as a key upstream regulator.

2010 ◽  
Vol 27 (2) ◽  
pp. 76-83 ◽  
Author(s):  
Kotaro Shimai ◽  
Yuki Kitaura ◽  
Yoshihiro Tamari ◽  
Takahito Nishikata

1993 ◽  
Vol 13 (7) ◽  
pp. 4400-4408
Author(s):  
T Kikuchi ◽  
K Raju ◽  
M L Breitman ◽  
T Shinohara

Regulatory sequences and nuclear factors governing tissue-restricted expression of the mouse arrestin gene were investigated. The results showed that while proximal promoter sequence positions -38 to +304 are sufficient to direct low levels of retina-specific gene expression, sequences extending upstream to position -209 support higher levels of expression in the retina, as well as detectable expression in the lens, pineal gland, and brain. Within the interval between positions -209 and -38, a broadly expressed nuclear factor, Bd, binds to sequences centered between positions -205 and -185, a region which contains two direct repeats of the hexamer, TGACCT. The proximal promoter binds three apparently retina-specific nuclear factors, Bp1, Bp2, and Bp3, through overlapping sequences centered between positions -25 and -15. Bp1 and Bp3 also recognize a closely related sequence found in the promoter regions of several other vertebrate photoreceptor-specific genes. Moreover, the consensus binding site for Bp1, designated PCE I, is identical to RCS I, an element known to play a critical role eliciting photoreceptor-specific gene expression in Drosophila melanogaster. The results suggest that PCE I and RCS I are functionally as well as structurally similar and that, despite marked differences in the fly and vertebrate visual systems, the transcriptional machinery involved in photoreceptor-specific gene expression has been strongly evolutionarily conserved.


Author(s):  
Robert W. Baloh

Josef Breuer presented his initial work on the inner ear to the Imperial Society of Physicians in 1873. His basic premise was that the semicircular canals sense angular movement of the head by movement of the fluid (endolymph) within them. The endolymph moves relative to the walls of the canals because of its inertia. In dissecting the semicircular canals of pigeons, he noted nerve endings contacting cells at the base of the ampulla and microscopic hairs extending from the top of the cells into a gelatinous bulb (the cupula). He hypothesized that movement of the endolymph fluid triggered by angular head movements bent the tiny hairs, activating the nerve endings at the base of the hair cells. The nerves in turn passed on signals reflecting the direction and magnitude of hair deflection to the central nervous system. At approximately the same time, Ernst Mach came to a similar conclusion.


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