Dataset Information

Hyperplastic discs differentially regulates the transcriptional outputs of hedgehog signaling.

ABSTRACT: Hedgehog (Hh) acts as a morphogen to activate the transcription of diverse target genes via its downstream effector Cubitus interruptus (Ci). Currently, it is less understood how Ci recruits co-factors to activate transcription. Here we report that hyperplastic discs (hyd), an E3 ubiquitin ligase, can differentially regulate the transcriptional outputs of Hh signaling. We show that loss of Hyd activity caused upregulation of some, but not all of Hh target genes. Importantly, Hyd does not affect the stability of Ci. Our data suggest that Hyd differentially restrains the transcriptional activity of Ci via selective association with respective promoters.

SUBMITTER: Wang G

PROVIDER: S-EPMC4351657 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Hyperplastic discs differentially regulates the transcriptional outputs of hedgehog signaling.

Wang Guolun G Tang Xiaofang X Chen Yujie Y Cao Jun J Huang Qinzhu Q Ling Xuemei X Ren Wenyan W Liu Songqing S Wu Yihui Y Ray Lorraine L Lin Xinhua X

Mechanisms of development 20140520

Hedgehog (Hh) acts as a morphogen to activate the transcription of diverse target genes via its downstream effector Cubitus interruptus (Ci). Currently, it is less understood how Ci recruits co-factors to activate transcription. Here we report that hyperplastic discs (hyd), an E3 ubiquitin ligase, can differentially regulate the transcriptional outputs of Hh signaling. We show that loss of Hyd activity caused upregulation of some, but not all of Hh target genes. Importantly, Hyd does not affect ...[more]

PMID: 24854243

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Project description:The process that partitions the nascent vertebrate central nervous system into forebrain, midbrain, hindbrain, and spinal cord after neural induction is of fundamental interest in developmental biology, and is known to be dependent on Wnt/β-catenin signaling at multiple steps. Neural induction specifies neural ectoderm with forebrain character that is subsequently posteriorized by graded Wnt signaling: embryological and mutant analyses have shown that progressively higher levels of Wnt signaling induce progressively more posterior fates. However, the mechanistic link between Wnt signaling and the molecular subdivision of the neural ectoderm into distinct domains in the anteroposterior (AP) axis is still not clear. To better understand how Wnt mediates neural AP patterning, we performed a temporal dissection of neural patterning in response to manipulations of Wnt signaling in zebrafish. We show that Wnt-mediated neural patterning in zebrafish can be divided into three phases: (I) a primary AP patterning phase, which occurs during gastrulation, (II) a mes/r1 (mesencephalon-rhombomere 1) specification and refinement phase, which occurs immediately after gastrulation, and (III) a midbrain-hindbrain boundary (MHB) morphogenesis phase, which occurs during segmentation stages. A major outcome of these Wnt signaling phases is the specification of the major compartment divisions of the developing brain: first the MHB, then the diencephalic-mesencephalic boundary (DMB). The specification of these lineage divisions depends upon the dynamic changes of gene transcription in response to Wnt signaling, which we show primarily involves transcriptional repression or indirect activation. We show that otx2b is directly repressed by Wnt signaling during primary AP patterning, but becomes resistant to Wnt-mediated repression during late gastrulation. Also during late gastrulation, Wnt signaling becomes both necessary and sufficient for expression of wnt8b, en2a, and her5 in mes/r1. We suggest that the change in otx2b response to Wnt regulation enables a transition to the mes/r1 phase of Wnt-mediated patterning, as it ensures that Wnts expressed in the midbrain and MHB do not suppress midbrain identity, and consequently reinforce formation of the DMB. These findings integrate important temporal elements into our spatial understanding of Wnt-mediated neural patterning and may serve as an important basis for a better understanding of neural patterning defects that have implications in human health.

Dataset Information

Hyperplastic discs differentially regulates the transcriptional outputs of hedgehog signaling.

Publications

Hyperplastic discs differentially regulates the transcriptional outputs of hedgehog signaling.

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