Publication for Zic1 and Zic2

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
mmu	Zic1	zinc finger protein of the cerebellum 1	22771			[link]
mmu	Zic2	zinc finger protein of the cerebellum 2	22772

Pubmed ID	Priority	Text
23606270	0.99	ZIC2 inhibits WNT/beta-catenin signaling through a direct interaction with TCF4 and ZIC proteins interact with GLI transcription factors to either suppress or enhance GLI-mediated transactivation.
	0.97	ZIC2 binding to TCF4 inhibits WNT signaling, so the combination of Axin2 expression and Zic expression may selectively modulate WNT signals from the dorsal hindbrain to the otocyst as well as restricting ventral WNT signals closer to the source of SHH.
	0.96	Zic1 and Zic2 expression, as well as strong Zic3 expression, was observed lateral to the developing inner ear (black arrowheads, Fig. 4L, 4M, 4N).
	0.96	Zic1 and Zic2 in mouse was seen in both the dorsal neural tube and in the mesenchyme surrounding the otic epithelium, while mesenchymal expression of Zic3-5 in mouse and Zic1-3 in chick was found only after the onset of expression in the neuroepithelium.
	0.94	Zic2 was the only Zic gene expressed surrounding the entire otic epithelium, including the developing basilar papilla (Fig. 5H), lateral semicircular canal (Fig. 5M), and the utricular and saccular maculae (Fig. 5R).
	0.93	Zic mutant mice examined to date, including Zic2kd/kd, Zic3Bn and Zic5-/- mutant mice.
	0.90	Zic1-3 expression was observed laterally around the outside of the otocyst (black arrowheads, Fig. 4G, 4H, 4I), and Zic1 and Zic2 expression was detected medially between the otic epithelium and the neural tube (yellow arrows, Fig. 4G, 4H).
	0.89	Zic1 and Zic2 (cf.
	0.85	Zic1 and Zic2 between the ventral neural tube and the otic epithelium overlapped with Tbx1 expression (cf.
	0.83	Zic1 expression was seen in cells located medially between the otic epithelium and the neural tube (Fig. 6N; a blue dashed line marks the border between otic epithelium and the surrounding mesenchyme), while Zic2- and Zic5-expressing cells surrounded the entire otic epithelium, although Zic5 was expressed more strongly adjacent to the dorsal region of the otic epithelium (Fig. 6O, 6R).
	0.74	Zic1 and Zic2 in the periotic mesenchyme at HH stage 18, whereas McMahon and Merzdorf only saw Zic2 expression in the periotic mesenchyme.
	0.67	Zic1-/-, all Zic2kd/kd, some Zic5-/-), making it impossible to detect signs of inner ear defects that affect the mature function of this sensory organ, such as changes in gait or posture, abnormal behaviors such as circling, and changes in the acoustic startle response or auditory brainstem responses (ABR).
	0.57	Zic1- and Zic2-expressing cells were found in the mesenchyme between the ventral neural tube and the otic epithelium and adjacent to the dorsolateral side of the otocyst at E9.5 and E10.5, although the Zic2-expressing cells were not seen as far ventrally as were the Zic1-expressing cells (yellow arrow and black arrowheads, Fig. 6B, 6C, 6H, 6I).
21211521	0.98	Zic2 and Zic1 are activated normally in Sonic Hedgehog-/- mutant embryos, Myf5 expression in newly forming somites is deficient in both Sonic Hedgehog-/- and in Zic2kd/kd mutant mouse embryos, providing further evidence that these Zic genes are upstream regulators of Hedgehog-mediated Myf5 activation.
	0.98	Zic2 mutant embryos until the time of Zic1 activation, and both Zic2 and Myf5 require Noggin for their activation.
	0.98	Zic1 or Zic2 alone transactivate the Myf5 ES enhancer luciferase reporter, and that their activities require a functional Gli binding site (Fig. 2A).
	0.98	Zic proteins have a weak affinity for Gli DNA binding sites, the transactivation activity of Zic1 and Zic2 alone is likely due to interactions of expressed Zic proteins with endogenously expressed Gli2.
	0.98	Zic1 and Zic2 have a functional role in Gli-dependent Myf5 regulation, likely through direct interactions with Gli1 and Gli2.
	0.98	Zic2 were co-expressed, 35% of the cells had Gli2 localized to the cytoplasm, 32% to both the cytoplasm and nucleus, and 33% to the nucleus, providing further evidence that Zic and Gli proteins functionally interact and suggesting that Zic2 promotes Gli function by promoting its nuclear localization.
	0.98	Zic1 and Zic2 are functionally redundant in Myf5 ES enhancer regulation (Fig. 2), the delayed activation of Myf5 in more mature somites of Zic2kd/kd embryos (Fig. 3E,F) is likely controlled by Zic1.
	0.98	Zic2 and Myf5 is delayed in newly formed somites until the 10th somite pair anterior to the PSM, when Zic1 also becomes activated (Fig. 6).
	0.98	Zic2 and Zic1, either through blocking BMP repression of Zic gene expression directly, or through blocking putative Zic activating signals, such as Wnts.
	0.97	Zic1, 2, and 3 transcripts are expressed in Myf5-expressing epaxial myogenic progenitors in the dorsal medial dermomyotome of newly forming somites, and immunohistological studies show that Zic2 protein is co-localized with Myf5 and Pax3 in the dorsal medial lip of the dermomyotome, but is not expressed in the forming myotome.
	0.97	Zic1 and Zic2, but not Zic3, potentiate the transactivation of Gli-dependent Myf5 epaxial somite-specific (ES) enhancer activity in 3T3 cells, and Zic1 activates endogenous Myf5 expression in 10T1/2 cells and in presomitic mesoderm explants.
	0.97	Zic1 and Zic2 transcripts are also expressed in the dorsal neural tube and in cells between the neural tube and dermomyotome in more anterior, mature somites, which are likely migratory neural crest cells (Fig. 1F, G, K).
	0.97	Zic1 or Zic2 with Gli1 or Gli2 further enhances transactivation by 5-7 fold and also requires a functional Gli binding site.
	0.97	Zic mutant embryos (Fig.3 O, P), indicating that Zic2 does not control Myf5 and MyoD activation through regulation of Pax3.
	0.97	Zic1-/-;Zic2kd/kd double homozygous mutant embryos die during early embryogenesis, but we also observed that Myf5 expression in Zic1+/- ;Zic2+/kd compound mutant embryos is diminished and delayed in the 6th to 9th most posterior somites of E9.25 embryos (n=3; Fig. 4 C, E), but is unaffected in heterozygous Zic2+/kd (n=5; Fig.4D) and Zic1+/- (n=4; data not shown) mutant embryos, consistent with the conclusion that Zic1 and Zic2 are functionally redundant for Myf5 regulation.
	0.96	Zic1 expression (A,B) is activated normally and Zic2 expression (C,D) is delayed in the posterior somites and overexpressed in the neural tube of Noggin-/- embryos.
	0.95	Zic1 and Zic2 transactivate the Myf5 ES enhancer and gene in NIH 3T3 and 10T1/2 cells and the presomitic mesoderm
	0.95	Zic1 and Zic2 are under independent regulation.
	0.93	Zic1 and Zic2 in Myf5 regulation and somite myogenesis
	0.93	Zic1 & Zic2 interact and functionally synergize with Gli1 & Gli2 in Myf5 activation
	0.93	Zic1 and Zic2 expression in Noggin-/- embryos.
	0.75	Zic1, Zic2, and Zic3 function in Myf5 regulation, we assayed their ability to transactivate Gli reporters in 3T3 cells, which express Gli2 and Gli3, but not Zic RNAs.
	0.73	Zic1 and Zic2 on endogenous Myf5 gene expression were investigated in 10T1/2 cells and posterior PSM explants from E9.5 mouse embryos.
25849986	0.98	Zic1 alone or in combination with Zic2 have a small cerebellum, indicating a requirement for the Zics in the normal proliferation of cerebellar GNPs.
	0.97	Zic1 or Zic2, or both together significantly reduced the expression of Grin2c compared with control-infected neurons (Fig. 7b).
	0.96	Zic1 or Zic2 knockdown tended to be up-regulated over the timecourse of CGN differentiation, whereas genes with higher expression following Zic1 or Zic2 knockdown tended to be down-regulated over differentiation.
	0.96	Zic1 or Zic2 knockdown is a shift in the gene expression program toward a less mature pattern.
	0.93	Zic1 or Zic2 knockdown on global gene expression in cultured CGNs.
	0.92	Zic1 or Zic2 drove significant changes in the expression of 81 and 147 genes, respectively (FDR < 0.10) (Supplementary Table 10).
	0.88	Zic1 and/or Zic2 expression in cultured CGNs (Supplementary Fig. 9a,b).
	0.75	Zic1 and Zic2 (Supplementary Fig. 9a,b).
22355535	0.98	Zic2/ZIC2 is a member of the Zic family of zinc finger proteins, which function as transcriptional regulators with critical roles in neural development.
	0.97	Zic family of proteins is highly conserved, Zic2 might function to expand the medial forebrain cholinergic neural progenitor cells by inhibiting their exit from the proliferating cell cycle in a manner analogous to that in the Zic1/Zic3 compound mutant mice.
	0.95	Zic2kd/+ mouse brain shows an altered morphology and reduction of forebrain cholinergic neurons and amygdalar Zic-positive cells
	0.91	Zic-binding sequence, Zic2-R409P showed lower binding affinity to the target sequences than wild-type Zic2 (Figure 6D and 6E).
	0.76	Zic2 mutations revealed that R409P was located within the highly conserved regions of the published Zic sequences, including those of the protostomians and cnidarians (Figure 6A and data not shown).
24929964	0.98	Zic1, and Zic2 (Figure 4E, Figure 4:figure supplement 1C).
	0.98	Zic1, and Zic2, promote neural gene expression and play roles in the derivation of the anterior neural plate.
	0.98	Zic1, and Zic2 genomic loci (Figure 4, Figure 4:figure supplement 1), indicating that Pou3f1 directly activates these neural fate-promoting genes.
	0.97	Zic1 and of Zic2, which are related to neural development, and of the BMP and Wnt signaling targets Id1 and Axin2 (Figure 4:figure supplement 1C).
29511358	0.98	Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage.
	0.97	Zic1 or Zic2 overexpression favored the generation of CR-positive interneurons at the expense of dopaminergic neurons.
	0.94	Zic1 and Zic2 in the control of neuronal differentiation of dorsal progenitors.
	0.84	Zic1 and Zic2, which in the embryo are restricted to medial aspects of the ventricular wall.
32117005	0.98	Zic1, Zic2, and Zic3 are expressed in the NPCs residing in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells.
	0.97	Zic1, Zic2, Zic3, Zic4, and Zic5) are expressed in the specific regions of neuroectoderm during the early embryonic phase in mice, and they have essential roles in CNS development.
	0.96	Zic1, Zic2, and Zic3 result in an inadequate division of forebrain, which fails to develop into two hemispheres.
32188872	0.98	Zic1, Zic2, Ntrk3, NGF, and BDNF) and neuronal (e.g., Gabra1, Gabra 2, and Glra2) genes were deregulated (Supplementary Fig. 1a,b).
	0.98	Zic1) and Zic2, were lower in Jdp2-KO GCPs (Supplementary Fig. 1), suggesting that Jdp2 might be required to control these GCP-specific genes transcriptionally.
	0.98	Zic1 and Zic2 are required for the development of the cerebellum, their downregulation in Jdp2-KO GCPs might be consistent with a cell proliferation that may result in the decrease of Atoh-1-positive GCPs during the process of development (Fig. 1a-d).
20199689	0.98	Zic proteins are present in the primitive meninx (meningeal cell precursors), and a deficiency of Zic2 or Zic1/Zic3 results in impaired proliferation and differentiation of meningeal precursors.
	0.98	Zic1 and Zic2 are strongly expressed in the embryonic meningeal cells and its precursors.
20826668	0.98	Zic1, Zic2 and Zic3 have overlapping patterns of expression and are essential for development of forebrain midline structures during embryogenesis .
	0.85	Zic1 and Zic2 but activation of the YFP reporter was not detected (Fig 1F-J, M-O and Fig 2B) suggesting that the Zic4-Cre transgene does not drive expression of Cre in these regions.
23028443	0.98	Zic2 is a prime candidate here: this transcription factor determines ipsilateral identity via regulation of EphB1 expression, and members of the Zic and Ten-m families have been shown to interact with each other.
	0.96	Zic2 is specific to the ipsilateral population, can regulate EphB1 expression and interactions between members of the Ten-m and Zic families have been reported (; see also below), it is feasible that Ten-m3 could impact ML mapping via alterations in EphB expression.
26382291	0.98	ZIC2 may be inhibiting craniofacial expression in the WT context and the lack of ZIC binding sites in the mutant enhancers may lead to disinhibition and activation of expression in craniofacial tissues.
	0.97	ZIC1 or 3 do not appear to be expressed in these structures, ZIC2 is expressed in the developing upper and lower jaws (Figure S1).
30297839	0.98	Zic2, another member of the Zic family, has been shown to increase the paraxial mesoderm progenitors at the primitive streak cooperatively with Zic3.
	0.95	Zic subtypes, Zic1 and Zic2, contribute differentially to vertebrate development.
31189106	0.98	ZIC1 and ZIC2 have been shown to play a role much later in development in the context of the neuronal gene expression program in cerebellar granule neurones.
	0.96	Zic1 and Zic4 are not expressed to appreciable levels, whereas Zic2 and Zic5 show progressively increased expression at d1 and d2 of the differentiation time course (Figure 2A).
19303920	0.98	Zic2 is both required and sufficient to alter the trajectory of retinal ganglion cell axons from crossed to uncrossed, lending support to our findings that Zic1 mediates MF divergence with respect to the brainstem ventral midline.
23665173	0.98	Zic genes function at the border of the neural plate to specify NC identity, and Zic2 is required for generation of the appropriate number of NC cells in mice.
25699711	0.98	Zic2, but not upon knockdown of Zic3, another Zic family member that is highly expressed in ES cells (Figures 3D-F).
26085810	0.98	Zic1 and/or Zic2 exhibit reduced cell proliferation and enhanced expression of motor neuron marker Wnt7a in the cerebellum.
28316121	0.98	zic2, and the Eh-1 domain is required for down-regulation of sox11 and zic1 in the neural ectoderm, these results demonstrate that in an intact embryo environment, mouse Foxd4 can up-regulate genes that maintain a proliferative, immature neural ectoderm and down-regulate genes that promote the transition to differentiating NPCs.
29207951	0.98	Zic1; Zics1-3 have all been shown to have an association with the ipsilateral retinal pathway, and Zic2 has been shown to play a critical role in the specification of laterality in RGCs.
29243319	0.98	zic2 transcription directly, and a role for Rfx4 as a direct activator of zic1 and zic3 has been proposed in mouse.
29391420	0.98	ZIC2 belongs to the Zic family of zinc finger proteins that play various critical developmental roles.
30557298	0.98	Zic1, Zic2, Zic4 that were highly expressed in WTM were severely down-regulated in HETM and KOM (Fig 6A).
31231187	0.98	Zic1 and Zic2.
31869353	0.98	Zic1 and Zic2 are both strongly expressed in differentiated cells of the hindbrain.
29187810	0.97	Zic2, Neurod2, Zic1, Prkcg, Grm4, Adcy1, and Homer3 in the dissected medulla oblongata of Hoxa5 cKO specimens (p-value <0.05; Table 1).
	0.97	Zic1, and Zic2 expression was detected in the LRN as Hoxa5 (Figure 5 and Table 2).
	0.96	Zic1, and Zic2 was observed in the PG and TRN, in a pattern overlapping with Hoxa5 expression (Figure 4 and Table 2).
	0.81	Zic1, and Zic2 in these nuclei (Figures 4C,F,I,L).
	0.68	Zic1, and Zic2-positive, while only a portion of Hoxa5-positive cells were Cbln1-positive (Figures 5C,F,I and data not shown).
25574472	0.97	Zic1, and Zic2 are seen.
	0.96	Zic1 (70.8%), Zic2 (28.3%), and GABAAR-alpha6 (50.6%) (Fig.1B and C).
	0.96	Zic1 and Zic2 were highly expressed at NS+8.
	0.96	Zic1 and Zic2.
30266956	0.97	Zic1 and Zic2 are expressed in the dorsal SVZ, where they act in inducing CalR+ PG interneurons while repressing a dopaminergic fate.
	0.97	Zic1 and Zic2 which have recently been reported to induce the generation of CalR+ interneurons while suppressing the dopaminergic fate of dorsal NSCs.
23471918	0.96	Zic1, Zic2 and Zic3 also contain a conserved region within the N-terminal portion of the protein called the ZOC motif.
	0.95	Zic2 that it is possible to produce a dominant-negative Zic molecule.
23612715	0.96	Zic1, Zic2, and Zic3 but expression of Zic1 and Zic2 gradually disappears during retinal development, while Zic3 expression continues into adulthood.
20553611	0.93	Zic1, Zic2, or Zic3 expression is compromised.
	0.88	zic1 and zic2 in Xenopus eyes, and zic2 and zic3 in chick eyes (this study).
21638761	0.93	Zic1 and Zic2 are prominently expressed in the mid-line of the developing cerebellum, and Zic1+/-Zic2+/Kd double heterozygous mice lack the primary fissure in the cerebellar vermis, the posterior superior fissure in the cerebellar hemispheres, a lobule in the anterior vermis, and have a truncation of the most posterior lobule.
30117627	0.74	Zic2-null mice have been found to have an inner ear development phenotype, although redundancy between Zic family members has not been thoroughly investigated.
29168327	0.73	Zic1-/- and Zic1+/-; Zic2+/- mice lack the superior posterior fissure in the anterior cerebellar hemisphere and Simplex and CrusI lobules are fused (Aruga, Inoue, Hoshino, & Mikoshiba, 2002).
31297611	0.64	Zic2, and Zic3 were not detected in d7 or d14 cells, and the homeobox genes Zic1 and Dlx5 were only expressed in the d7 cells, despite these having been reported in the NC of a range of species (Table 2); however, Meis homeobox 2 (Meis2) was expressed in both d7 and d14 cells.