A novel role for zebrafish zic2a during forebrain development

Sanek, Nicholas A.; Grinblat, Yevgenya

doi:10.1016/j.ydbio.2008.02.029

Cited by 23 publications

(26 citation statements)

References 75 publications

(101 reference statements)

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“…2G). zic2a is expressed in the telencephalon and dorsal diencephalon (Sanek and Grinblat, 2008) (see Fig. S2 in the supplementary material), consistent with the possibility that Zic2a could act cellautonomously, and perhaps directly, to repress six3b in these cells.…”

Section: Research Articlesupporting

confidence: 66%

“…To determine whether six3b transcription is regulated by Zic2a in zebrafish, we employed antisense MO knockdown assays as previously described (Nyholm et al, 2007;Sanek and Grinblat, 2008). Zebrafish six3b is expressed in the anterior forebrain primordium from early somitogenesis (Seo et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

“…S2 in the supplementary material), suggesting that Zic2a functions indirectly in this area. As shha expression appears to be unaffected in Zic2a-depleted embryos (Sanek and Grinblat, 2008), we hypothesized that Zic2a might control transcription of a secreted factor that acts as an Hh agonist or antagonist to modulate the transcriptional activation of six3b. This hypothesis predicts that expression of six3b should be enhanced in zic2a morphants in an Hh signaling-dependent manner.…”

Section: Research Articlementioning

confidence: 99%

“…Mutations in mammalian ZIC2 can cause HPE (Brown et al, 1998), and the zebrafish ortholog zic2a is required for correct formation of the ventral diencephalon (Sanek and Grinblat, 2008). In the developing retina, Zic2 and other Zic family members are required for retinal axon guidance in mouse and chick (Herrera et al, 2003;Zhang et al, 2004;.…”

Section: Introductionmentioning

confidence: 99%

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Zebrafishzic2apatterns the forebrain through modulation of Hedgehog-activated gene expression

et al. 2009

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Holoprosencephaly (HPE) is the most common congenital malformation of the forebrain in human. Several genes with essential roles during forebrain development have been identified because they cause HPE when mutated. Among these are genes that encode the secreted growth factor Sonic hedgehog (Shh) and the transcription factors Six3 and Zic2. In the mouse, Six3 and Shh activate each other's transcription, but a role for Zic2 in this interaction has not been tested. We demonstrate that in zebrafish, as in mouse, Hh signaling activates transcription of six3b in the developing forebrain. zic2a is also activated by Hh signaling, and represses six3b non-cell-autonomously, i.e. outside of its own expression domain, probably through limiting Hh signaling. Zic2a repression of six3b is essential for the correct formation of the prethalamus. The diencephalon-derived optic stalk (OS) and neural retina are also patterned in response to Hh signaling. We show that zebrafish Zic2a limits transcription of the Hh targets pax2a and fgf8a in the OS and retina. The effects of Zic2a depletion in the forebrain and in the OS and retina are rescued by blocking Hh signaling or by increasing levels of the Hh antagonist Hhip, suggesting that in both tissues Zic2a acts to attenuate the effects of Hh signaling. These data uncover a novel, essential role for Zic2a as a modulator of Hh-activated gene expression in the developing forebrain and advance our understanding of a key gene regulatory network that, when disrupted, causes HPE.

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Section: Research Articlesupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Research Articlementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Zebrafishzic2apatterns the forebrain through modulation of Hedgehog-activated gene expression

et al. 2009

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“…The role of Zic4 is not well understood, but Zic1 activity is required to maintain EGL cells in a progenitor state [57,58], although a direct role in the reception of Shh signaling has not been established. A diminishment in Shh-dependent granule neuron progenitor proliferation in ZIC1/4-dependent DWM may account for the cerebellar hypoplasia seen in these DWM patients, however, Zic functions that are Shhindependent may also contribute to the DWM phenotype [59,60], distinguishing DWM from JSRD. The study of Zic mouse models in ongoing, as is the search for additional human DWM causative genes [61].…”

Section: Dandy-walker Malformation and Cerebellar Vermis Hypoplasiamentioning

confidence: 99%

Cerebellar development and disease

Millen¹,

Gleeson²

2008

Current Opinion in Neurobiology

171

141

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The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitterspecific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum.

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Zebrafish Zic Genes Mediate Developmental Signaling

Winata

Korzh

2018

Advances in Experimental Medicine and Biology

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The introduction of genomics into the field of developmental biology led to a vast expansion of knowledge about developmental genes and signaling mechanisms they are involved in. Unlike mammals, the zebrafish features seven Zic genes. This provides an interesting insight into Zic gene evolution. In addition, an unprecedented bioimaging capability of semitransparent zebrafish embryos turns to be a crucial factor in medium- to large-scale analysis of the activity of potential regulatory elements. The Zic family of zinc finger proteins plays an important, relatively well-established, role in the regulation of stem cells and neural development and, in particular, during neural fate commitment and determination. At the same time, some Zic genes are expressed in mesodermal lineages, and their deficiency causes a number of developmental defects in axis formation, establishing body symmetry and cardiac morphogenesis. In stem cells, Zic genes are required to maintain pluripotency by binding to the proximal promoters of pluripotency genes (Oct4, Nanog, Sox2, etc.). During embryogenesis, the dynamic nature of Zic transcriptional regulation is manifested by the interaction of these factors with distal enhancers and other regulatory elements associated with the control of gene transcription and, in particular, with the Nodal and Wnt signaling pathways that play a role in establishing basic organization of the vertebrate body. Zic transcription factors may regulate development through acting alone as well as in combination with other transcription factors. This is achieved due to Zic binding to sites adjacent to the binding sites of other transcription factors, including Gli. This probably leads to the formation of multi-transcription factor complexes associated with enhancers.

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A novel role for zebrafish zic2a during forebrain development

Cited by 23 publications

References 75 publications

Zebrafishzic2apatterns the forebrain through modulation of Hedgehog-activated gene expression

Zebrafishzic2apatterns the forebrain through modulation of Hedgehog-activated gene expression

Cerebellar development and disease

Zebrafish Zic Genes Mediate Developmental Signaling

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