Requirements for Neurogenin2 during mouse postnatal retinal neurogenesis

Kowalchuk, Angelica M.; Maurer, Kate A.; Shoja‐Taheri, Farnaz; Brown, Nadean L.

doi:10.1016/j.ydbio.2018.07.020

Cited by 12 publications

(12 citation statements)

References 111 publications

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“…The anti-Ngn2 antibody was raised against a recombinant protein of the N-terminal basic helix-loop-helix domain of mouse Ngn2 ( Lo et al, 2002 ). It specifically detects Ngn2 in Western blots of embryonic mouse cortices ( Ge et al, 2006 ), but does not produce immunolabeling in the retinae of postnatal Ngn2 knock-out mice ( Kowalchuk et al, 2018 ). Correspondingly, this antibody has been successfully used to characterize epibranchial neurogenesis in mice ( Washausen and Knabe, 2013 , 2018 ; Zhang et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Washausen

Knabe

2021

Front. Cell Dev. Biol.

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Placodes are ectodermal thickenings of the embryonic vertebrate head. Their descendants contribute to sensory organ development, but also give rise to sensory neurons of the cranial nerves. In mammals, the signaling pathways which regulate the morphogenesis and neurogenesis of epibranchial placodes, localized dorsocaudally to the pharyngeal clefts, are poorly understood. Therefore, we performed mouse whole embryo culture experiments to assess the impact of pan-fibroblast growth factor receptor (FGFR) inhibitors, anti-FGFR3 neutralizing antibodies or the pan-bone morphogenetic protein receptor (BMPR) inhibitor LDN193189 on epibranchial development. We demonstrate that each of the three paired epibranchial placodes is regulated by a unique combination of FGF and/or bone morphogenetic protein (BMP) signaling. Thus, neurogenesis depends on fibroblast growth factor (FGF) signals, albeit to different degrees, in all epibranchial placodes (EP), whereas only EP1 and EP3 significantly rely on neurogenic BMP signals. Furthermore, individual epibranchial placodes vary in the extent to which FGF and/or BMP signals (1) have access to certain receptor subtypes, (2) affect the production of Neurogenin (Ngn)2+ and/or Ngn1+ neuroblasts, and (3) regulate either neurogenesis alone or together with structural maintenance. In EP2 and EP3, all FGF-dependent production of Ngn2+ neuroblasts is mediated via FGFR3 whereas, in EP1, it depends on FGFR1 and FGFR3. Differently, production of FGF-dependent Ngn1+ neuroblasts almost completely depends on FGFR3 in EP1 and EP2, but not in EP3. Finally, FGF signals turned out to be responsible for the maintenance of both placodal thickening and neurogenesis in all epibranchial placodes, whereas administration of the pan-BMPR inhibitor, apart from its negative neurogenic effects in EP1 and EP3, causes only decreases in the thickness of EP3. Experimentally applied inhibitors most probably not only blocked receptors in the epibranchial placodes, but also endodermal receptors in the pharyngeal pouches, which act as epibranchial signaling centers. While high doses of pan-FGFR inhibitors impaired the development of all pharyngeal pouches, high doses of the pan-BMPR inhibitor negatively affected only the pharyngeal pouches 3 and 4. In combination with partly concordant, partly divergent findings in other vertebrate classes our observations open up new approaches for research into the complex regulation of neurogenic placode development.

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Section: Methodsmentioning

confidence: 99%

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Washausen

Knabe

2021

Front. Cell Dev. Biol.

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“…For example, YAP functions as an essential regulator of RPE regional specification at developing OV stages, which absent leads to prospective RPE transdifferentiates into NR, thus inducing retinal duplication (H. Zhang et al, 2012). Unlike previous study, the Chx10-Cre line used here deletes genes merely in the E9-P2 RPCs (Kowalchuk et al, 2018), our existing data suggest that YAP deficiency in RPCs at this stage is not sufficient to cause significant retinal structural damage, implying a more cryptic function of YAP at earlier stages in ocular development. The potential mechanisms of YAP in retinal development warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate the underlying role of YAP specifically in embryonic and adult mouse retina, we developed Yap1 conditional knockout mice by crossing Yap1 exon 1-2 floxed mice (Yap1 flox/flox ) with BAC-Tg Chx10-Cre mice (Figure S1a), which droves Cre expression in the majority of E9-P2 RPCs, as well as in a subset of retinal Müller cells at adult stage (Kowalchuk et al, 2018;Lu et al, 2013;Ueki et al, 2009). Their progenies were intercrossed to yield littermate Yap1 flox/flox ; Chx10-Cre (hereafter Yap1 ChxKO ), Yap1 flox/ + ; Chx10-Cre (hereafter Yap1 Het ) and Yap1 flox/flox (hereafter Yap1 Ctrl , served as control) mice (Figure S1b).…”

Section: Generation Of Yap1 Conditional Knockout Mice Using Chx10-cre...mentioning

confidence: 99%

Specific ablation of Hippo signalling component Yap1 in retinal progenitors and Müller cells results in late onset retinal degeneration

Yang

Jiang

Xiao

et al. 2022

Journal Cellular Physiology

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Yes-associated protein (YAP) is a major component of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense YAP1 mutations in humans result in autosomal dominant coloboma. Here, we generated a conditional knockout mouse model in which Yap1 was specifically deleted in embryonic retinal progenitor cells (RPCs) and in mature Müller cells using a Chx10-Cre driver. Our data demonstrated that the conditional ablation of Yap1 in embryonic RPCs does not prevent normal retinal development and caused no gross changes in retinal structure during embryonic and early postnatal life. Nevertheless, Yap1 deficient in retinal Müller cells in adult mice leads to impaired visual responses and extensive late-onset retinal degeneration, characterized by reduced cell number in all retinal layers. Immunofluorescence data further revealed the degeneration and death of rod and cone photoreceptors, bipolar cells, horizontal cells, amacrine cells and ganglion cells to varying degrees in aged knockout mice. Moreover, alteration of glial homeostasis and reactive gliosis were also observed. Finally, cell proliferation and TUNEL assay revealed that the broad retinal degeneration is mainly caused by enhanced apoptosis in late period. Together, this work uncovers that YAP is essential for the normal vision and retinal maintenance, highlighting the crucial role of YAP in retinal function and homeostasis.

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“…Our finding that Atoh7 regulates multiple component genes of the Notch pathway fits this model. Multiple bHLH transcription factors are involved in distinct retinal cell fates, Atoh7 and Neurog2 in RGCs, Neurod1 and Neurod4 in PHCs, and Bhlhe22 and Ptf1a in H&As 18,[75][76][77][78][79][80][81] . The distinct functions of these bHLH factors are also manifested by the cross repression between some of these genes.…”

Section: Discussionmentioning

confidence: 99%

“…In the early embryonic retina, multiple bHLH transcription factors, including Atoh7, Neurod1, Neurog2, Olig2, Ptf1a, Bhlhe22, and Ascl1, which all binds to the E box motif, are expressed in tRPCs. These bHLH factors all have distinct roles in retinal cell differentiation 18,[75][76][77][78][79][80][81] . Consistent with these bHLH factors functioning in retinal cell differentiation, the E box motifs were not enriched in the nRPCs, but continued to be enriched in early RGCs (but not late RGCs), H&As, and PHCs (Figure 4A, B).…”

Section: The Epigenetic Landscape In Transitional Rpcsmentioning

confidence: 99%

Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation

Cheng

Nan

et al. 2022

Preprint

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During development, all retinal cell types emerge from multipotent retinal progenitor cells (RPCs) following distinct trajectories. Each lineage is subject to regulation by multiple intrinsic and extrinsic factors, which converge onto the epigenetic landscape to dictate the collective gene expression profile and thereby the phenotypes of individual cell states/types. Recent scRNA-seq studies have further delineated these trajectories, providing a general picture of the relationships between the different cell states/types and revealing a transitional RPC state shared by all the early lineages. Nevertheless, how the epigenetic landscape shifts along individual trajectories is only beginning to be disseminated, and the roles of key transcription factors in these shifts are not known. In this study, we dissect the changes of the epigenetic landscape along these trajectories in the early developing retina by scATAC-seq and identify globally the enhancers, enriched motifs, and potential interacting transcription factors underlying the cell state/type specific gene expression in individual lineages, with a focus on retinal ganglion cells (RGCs). Using CUT&Tag-seq, we further identify the enhancers bound directly by four key transcription factors, Otx2, Atoh7, Pou4f2, and Isl1, and uncover their roles in shaping the epigenetic landscape to control gene expression in a sequential and combinatorial fashion during RGC genesis. These results provide experimental support for a general paradigm in which transcription factors collaborate and compete to regulate the emergence of distinct retinal cell types such as RGCs from the multipotent transitional RPCs.

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Requirements for Neurogenin2 during mouse postnatal retinal neurogenesis

Cited by 12 publications

References 111 publications

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Specific ablation of Hippo signalling component Yap1 in retinal progenitors and Müller cells results in late onset retinal degeneration

Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation

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